Since most of the initial symptoms of solitary vestibular schwannomas (VS) are auditory symptoms such as hearing loss and tinnitus, our principal research theme has been how we can improve the prognosis of VS patients from the standpoint of otologists. As more and more tumors are detected at an early stage as small tumors, our goal is to preserve hearing function and QOLs in VS patients. Specifically, we have promoted surgery by transpetrosal approach with intraoperative continuous nerve monitoring, clarified the indications for hearing conservation surgery considering preoperative OAE and ABR results, and improved the hearing conservation rate. In a multicenter, retrospective observational study, we found that acute sensorineural hearing loss in VS is characterized by recurrence in 25% of the patients by one year. Besides, we standardized the Japanese version of the VS-specific QOL questionnaire, and found that the severity of tinnitus had a significant impact on the decline in QOL in VS patients during follow-up, and established a strategy to deal with post-operative tinnitus. Thereafter, we continue to conduct research to improve the prognosis further.
Recent advances in next-generation sequencing have given rise to new challenges because of difficulties in variant pathogenicity interpretation and large dataset management, including many kinds of public population databases and public or commercial disease-specific databases. We developed a database software for improving clinical next-generation sequencing workflow through the unified management of variant information and clinical information. Based on this database software, we developed a central database system to manage the over 12,000 target re-sequencing analysis results and clinical information associated with the Japanese nation-wide deafness gene study consortium. This database is a powerful tool for genetic testing, especially for the variant pathogenicity classification based on large number of patients data.
We will also present the newly developed copy number analysis tool for social health insurance based genetic testing platform. Using this software, we performed the copy number analysis of a large Japanese hearing loss cohort (2,475 patients) and identified many gene copy number variants. The most prevalent copy number variation was STRC gene copy number loss, with 129 patients carrying this copy number variation.
Thus far, more than 120 causative genes for hereditary hearing loss have been discovered. The remarkable progress in DNA sequencing technology has contributed to this discovery. Massively parallel DNA sequencing using next-generation sequencing (NGS) has emerged as a standard for genetic testing, plays an important role, provides rapid genetic diagnosis, and improves the diagnostic rate. However, NGS detects a huge number of variants, and adequate knowledge is needed to evaluate their pathogenicity. The pathogenicity of the identified variants is classified into pathogenic, likely pathogenic, uncertain significant, likely benign, and benign according to the American College of Medical Genetics and Genomics guidelines. A variant with uncertain significance has a broad pathogenicity, ranging from 10% to 90%. Therefore, careful genetic counseling regarding the pathogenicity of the variant is required. Moreover, we should not interpret that a genetic factor is not related to the hearing loss when no apparent causative variant is detected on genetic testing.
In Japan, genetic testing in patients with congenital hearing loss is covered by Social Health Insurance. The screening by genetic testing is performed nationwide to identify the causes of hearing loss and to provide optimal medical treatment. The benefits of genetic testing include 1) elucidating the cause of hearing loss, 2) predicting the severity and prognosis of hearing loss and foreseeing accompanied symptoms, such as dizziness and diabetes, and 3) providing helpful information to choose treatment options, such as cochlear implantation. Between October 2012 and May 2020, we performed genetic testing in 132 patients with pre-lingual hearing loss, and the overall diagnostic rate was 41.7% (56 of 132 patients with congenital hearing loss, 47 of 119 families). Genetic testing for congenital hearing loss is a very useful tool for early decision making, particularly in case of simultaneous bilateral cochlear implantation. It is also useful in determining the timing of cochlear implant surgery in patients with progressive sensorineural hearing loss. Even post genetic diagnosis, it is important to carefully follow up the changes in hearing levels.
Among patients with idiopathic bilateral sensorineural hearing loss, seven causative genes that develop late-onset hearing loss under the age of 40 were identified and defined as juvenile onset bilateral sensorineural hearing loss; this hearing loss is clearly different from age-related hearing loss. The genes are ACTG1, CDH23, COCH, KCNQ4, TECTA, TEMPRSS3, and WFS1. If the patients have severe to profound hearing loss (70 dB or more), they can be extrapolated as intractable diseases. For patients with juvenile onset bilateral sensorineural hearing loss, genetic testing with next-generation sequencers and genetic counseling are accompanied with autonomous options ranging from hearing aids to hearing implants, which has become very beneficial.
Usher syndrome is a communication disorder characterizes by hearing loss and visual impairment. The Health and Labour Sciences Research Grants program continues to carry out research on Usher syndrome. The surveillance study group of refractory hearing loss is currently investigating Usher syndrome. Usher syndrome is classified into three types according to the stages and symptoms of sensorineural hearing loss and retinitis pigmentosa. However, clinical diagnosis has limitations. The genetic test is useful for confirming the diagnosis. At the end of March, 2020, 204 samples were registered across Japan. Patients in which congenital hearing loss and retinitis pigmentosa occurred in the first decade were the most frequent. MYO7A and CDH23 gene mutations were the most frequent in Type 1, while the USH2A gene mutation was the most frequent in Type 2. The diagnosis posed by the genetic test is important; because there are variation of hearing loss by the same causative gene.
In the next-generation sequencing era, accurate diagnosis of rare syndromic hearing loss has become available.
In this study, we examined the significance of early diagnosis of syndromic hearing loss using data from cases in which gene mutations causing syndromic hearing loss were identified by genetic analysis studies of hearing loss conducted in collaboration with Shinshu University.
Early diagnosis of syndromic hearing loss using comprehensive genetic testing is useful not only for early initiation of treatment for accompanying symptoms but also for providing necessary information for the treatment of hearing loss, such as cochlear implant surgery. In addition, predicting the problems that can be caused by accompanying symptoms before their onset may lead to a revision of the support system for education. In conclusion, there are various merits for early diagnosis of rare syndromic hearing loss before the expression of accompanying symptoms by comprehensive analysis using next-generation sequencing.
This study aimed to reveal the patency of the anterior epitympanic space (AES) and the surgical outcomes after transcanal endoscopic ear surgery (TEES) for attic cholesteatoma with a classification of anatomical variation of the AES. A total of 74 ears [72 patients with early-stage (I or II) attic cholesteatoma] underwent TEES and then analyzed. The tensor fold in the AES anatomical classification, the postoperative patency of the AES evaluated using computed tomography images, and hearing outcomes were evaluated after TEES for early-stage attic cholesteatoma. There were 14 (18.9%) ears with a vertical tensor fold orientation, 29 (39.2%) ears with an oblique orientation, and 29 (39.2%) ears with a horizontal orientation. The total patency rate in the AES was 81.0%, without any significant difference in the anatomical variation in the AES. Cholesteatoma recurrence was observed in 3 cases (4.1%), all of which had obstructed AES. No significant difference was found in the postoperative air-bone gap regardless of the patency of the AES.
Objectives: We aimed to determine vestibular nerve function in patients with auditory neuropathy (AN) based on galvanic vestibular-evoked myogenic potentials (VEMPs).
Methods: We enrolled 8 patients with an average age of 45.3 ± 29.5 y (mean ± standard deviation) diagnosed with AN. We evaluated their vestibular nerve function based on galvanic VEMPs. The function of the semicircular canals was assessed in all patients using a caloric test. The function of the otolithic apparatus was evaluated using cervical VEMPs.
Results: Galvanic VEMPs were assessed in 8 patients with AN; 4 patients (50%) had bilateral inaction. Six patients showed no responses in the caloric test and cervical VEMPs.
Conclusion: In this study, the response of galvanic VEMPs was reduced in 50% of the subjects. Therefore, in some patients with AN, the function of the vestibular nerve is compromised.
Tympanic perforation closure mainly prevents otorrhea and improves hearing. The success of the pediatric tympanic perforation treatment is presumed to be related to surgery type, age, reason of perforation, and eustachian tube function. In this study, we analyzed 75 cases of tympanic perforation consisting of 92 ears of children. We reported the relationship between surgery type, age, perforation size, eustachian tube function, tympanic membrane closure rate, and pre- and post-operative hearing. We concluded that the closure rate was good both in tympanoplasty and myringoplasty, and it was better at age ≥ 12 years than age <12 years. However, post-operative hearing tended to improve in children under 12 years of age than in older children, and low-frequency hearing was good regardless of the size of tympanic perforation.
The course of subjective hearing ability and pathology of malformation were examined in adults (17 ears) who underwent surgery for ossicular malformation at the Department of Otolaryngology, Yamaguchi University Hospital between April 1999 and December 2013. The patients noticed a pre-existing hearing loss in 13 of 17 ears and recently noticed a hearing loss in the other 4 ears. In the group of patients who had noticed hearing loss for some time, progression of hearing loss was recognized in 4 ears, and the degree of hearing loss remained unchanged for 9 ears. The pathology of malformation was examined by dividing the patients into two groups: those who were aware of the progression of hearing loss (group of progressive hearing loss: 8 ears) and those whose hearing loss remained unchanged (group of fixed hearing loss: 9 ears). In the group of progressive hearing loss, there were discontinuities in the incus, stapes superstructure, or stapes footplate in all cases. On the other hand, in the group of fixed hearing loss, fixation of the malleus, incus, or stapes footplate was observed in many cases. In cases wherein patients recently noticed a hearing loss (4 ears), the possibility of the progression of discontinuities in the incus, stapes superstructure, or stapes footplate was considered.
Although acute mastoiditis is a severe infection that may lead to subperiosteal abscesses and intracranial complications, the necessity and procedure of surgical treatment for acute mastoiditis remain controversial. In this study, we discuss the management of acute mastoiditis, including surgical treatment, based on our experiences in 5 cases and 6 ears, as well as a literature review.
All patients initiated receiving intravenous antibiotics on admission. Four of the 5 cases involved complications on admission: meningitis in two cases and a periauricular abscess or cellulitis in two cases. Although one patient had no complications, intravenous antibiotics were ineffective. Therefore, we performed middle ear surgery in all cases to control for the source of infection. Almost all patients underwent surgery within 3 days of admission. The procedures were intact canal wall tympanomastoidectomy in 4 cases and 4 ears and simple cortical mastoidectomy in 2 cases and 2 ears. In all cases, the attic and aditus ad antrum occupied granulous tissue, which blocked the root from the attic to the mesotympanum. Communication was created between the attic and mesotympanum due to the thorough removal of the granulous tissue. The postoperative courses were favorable in all cases without the recurrence of mastoiditis.
It is important to prevent the progression of mastoiditis due to middle ear surgery, including mastoidectomy at an early stage, in cases of acute mastoiditis with complications and cases without complications for which antibiotics are not effective.
Mucosal melanomas occur most commonly in head and neck lesions. We report a case of Eustachian tube (ET) mucosal melanoma diagnosed based on the cytological findings of dark middle ear effusion. The patient was a 44-year-old woman who presented with glue ear for 2 months. Tympanostomy and tube insertion were performed, but the dark effusion persisted, similar to cases of cholesterol granuloma. We also found a small dark mass at the pharyngeal orifice of the ET. The same dark lesion was not observed in the middle ear mucosa. Temporal bone computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT demonstrated a limited mass in the ET and middle ear effusion. Melanophages were present in the dark middle ear effusion, which was positively stained with Fontana–Masson stain as the cytological findings. Immunohistochemical analysis showed positive reactivity of atypical cells with S-100 and HMB-45 antibodies. She was treated with carbon ion radiotherapy and chemotherapy (DAV), but multiple brain metastases were found after 1 year.
Cytological diagnoses of middle ear effusion in mucosal melanoma of the temporal bone have not been reported in the previous literature. A similar examination has been previously used for cerebrospinal fluid, ascites, and pleural effusion. New chemotherapies, such as checkpoint inhibitors, and increasing insurance coverage of carbon ion radiotherapy will improve the treatment rate. This case yielded a disappointing result, but cytological examination of the middle ear effusion may be a useful and safe method for early diagnosis.
Non-tuberculous mycobacteria (NTM) or mycobacteria other than Mycobacterium tuberculosis are widely distributed in the environment, such as soil and water. Mycobacterium abscessus is an extensively drug-resistant opportunistic NTM that can cause chronic otitis media. We present the case of a 25-year-old woman with M. abscessus-mediated chronic suppurative otitis media. Following treatment with systemic antibiotic therapy, including clarithromycin for 6 months, she underwent tympano-mastoidectomy to improve her hearing and confirm the elimination of the pathogen. Further, we identified 119 similar cases reported in the literature and collected detailed information from 34 articles in the PubMed database. The infection route of M. abscessus, necessity of surgical debridement, selection of antimicrobial agents, duration of antibiotic therapy, and hearing prognosis were reviewed.