Right Incus Osteoma in a Child: A Differential Diagnosis of Middle Ear Malformations.

Osteomas of the temporal bone, especially those involving the incus, are rare, unilateral, benign osseous tumors. The clinical presentation is usually isolated conductive hearing loss, and the diagnosis is confirmed by a temporal computed tomography scan. Osteomas of the incus represent a differential diagnosis of congenital middle ear malformations in children, which are the most frequent cause of conductive hearing loss with a normal eardrum in the pediatric population. In case of disabling symptomatology, surgery seems to be a safe way to recover normal hearing.

Double Ring in Cochlear Otosclerosis: A Limit to Cochlear Implantation? The Solution Is the Surgical Approach.

We present a case of a 50-year patient with a severe form of otosclerosis (double ring) that was successfully implanted. We used a bone-anchored hearing implant for restoring the hearing in the right side and a cochlear implant in the left side; both surgeries did not show any complications. For reducing the risk of a secondary bone ossification related to the trauma of cochleostomy for electrode's insertion, we used a round window approach. The patient recovered a normal auditory threshold and normal speech perception capacity both in silence and noise conditions 1 year after surgery.

Optimizing Management of Otophyma: A Case Series Highlighting the Role of Surgical and Retinoid Therapy.

Otophyma is a rare condition that can result in conductive hearing loss. Current otophyma literature does not examine validated treatment outcomes for patients. Utilizing a medical and surgical approach to maintain a patent canal can lead to significant objective improvements. The aim of this case series is to describe a combined successful approach in 3 cases from an academic, multidisciplinary center. The main outcomes analyzed were pre and post air-bone gap audiogram analysis and disimpaction frequency. The results showed that post-management, patient 1 had substantial improvement in hearing, recovering 49 dB in his right ear and 25 dB in his left ear, demonstrating near complete air-bone gap closure. Patient 2 showed a similar dermatologic and functional improvement, although objective audiometric assessment related to otophyma could not be performed due to coexisting chronic otitis media and cholesteatoma. Patient 3, in the 12 months prior to comanagement, had 8 bilateral disimpactions, and following comanagement had 2 disimpactions in 23 months. All 3 patients were pleased with the resultant functional and physical appearance following comanagement. By presenting this approach and objective measures of treatment, we hope to improve future clinical decision-making in a rare condition.

New Imaging Findings of Incomplete Partition Type III Inner Ear Malformation and Literature Review.

Incomplete partition type III, also referred to as X-linked deafness, is a rare genetic inner ear malformation. Its characteristic CT findings, including bulbous dilation of the internal auditory canal and absence of the modiolus with the interscalar septa present, have been well-recognized. In this series of 19 cases, we report the abnormalities of the vestibule and semicircular canals and provide a comprehensive description of their CT and MR imaging findings. The inner ear malformations in incomplete partition type III were bilateral and basically symmetric, with involvement of the internal auditory canal, nerve canals in the fundus, cochlea, vestibule, semicircular canals, vestibular aqueduct, otic capsule, round window, oval window, and stapes. An irregular vestibule with a cystic appearance is also a distinctive imaging feature, which could be seen in about 90% of our patients, with a cystic appearance of the semicircular canals present in nearly half of the cases.

Tophaceous Gout of the Middle Ear: Case Reports and Review of the Literature.

Tophaceous gout of the middle ear is a rare occurrence that presents as a granular white-colored mass. It is frequently misdiagnosed as cholesteatoma or tympanosclerosis in patients who otherwise may not manifest any clinical or biochemical signs of gout. While uncommon, it can lead to clinically significant disease such as conductive hearing loss. The present report describes 2 cases of middle ear gouty tophi initially mistaken for another entity. Both patients underwent surgery, and the diagnosis of gout was revealed after final histopathological analysis. A review of the literature is also presented.

Audiometric Results of Stapedotomy Surgery for Otoscelorsis: Influence of the Radiological Stage.

BACKGROUND: The objective of this study was to identify a correlation between the radiological stage of otosclerosis and the pre- and postoperative audiometric results of patients who underwent a stapedotomy. METHODS: Ninety-three patients with radiologically and surgically confirmed otosclerosis who underwent stapedotomy surgery and CT scanning within 18 months before the operation were included. The CT scans were interpreted by an otologist and a specialised radiologist to determine their radiological stage according to the classification of Veillon and Fraysse. The patients received a pre- and postoperative audiogram in the short and long term. RESULTS: The preoperative bone conduction thresholds were higher in patients who presented with an advanced radiological stage of otosclerosis: 32.7 dB ±â€Š12.4 compared with those who presented with a less advanced radiological stage: 24.3 dB ±â€Š10.0. The preoperative air conduction thresholds were higher in patients who presented with an impairment of the round window: 58.1 dB ±â€Š13.5 compared with those who presented with no impairment of the round window: 48.7 dB ±â€Š14.5. The postoperative improvement in the air-bone gap was significantly higher for the localised foci: 16.9 dB ±â€Š8.6 versus 11.0 dB ±â€Š9.2, but only in the short term. CONCLUSION: There was a clinical radiological correlation with the preoperative results: In BC, there was a correlation with the radiological stage of Veillon and in AC, there was a correlation with impairment of the round window. The link between the radiological stage of otosclerosis and the postoperative audiometric results is less obvious. In the short term, the audiometric improvements in the air-bone gap were greater in patients in the early stages according to the Veillon classification, but this result was not sustained in the long-term.

Association of Hearing Loss and Otologic Outcomes With Fibrous Dysplasia.

Importance: Fibrous dysplasia (FD) and McCune-Albright syndrome (MAS) are rare bone and endocrine disorders in which expansile fibro-osseous lesions result in deformity, pain, and functional impairment. The effect of FD on hearing and otologic function has not been established. Objectives: To characterize audiologic and otologic manifestations in a large cohort of individuals with FD/MAS and to investigate potential mechanisms of hearing loss. Design, Setting, and Participants: In this natural history study, individuals with craniofacial FD seen at a clinical research center underwent clinical, biochemical, computed tomographic, audiologic, and otolaryngologic evaluations. Main Outcomes and Measures: Clinical and radiologic features associated with hearing loss and otologic disease were evaluated. Conductive hearing loss was hypothesized to be associated with narrowing of the external auditory canal (EAC), FD involving the epitympanum, and FD crowding the ossicular chain. Sensorineural hearing loss was hypothesized to be associated with FD affecting the internal auditory canal (IAC) and otic capsule. Results: Of the 130 study participants with craniofacial FD who were evaluated, 116 (89.2%) had FD that involved the temporal bone (median age, 19.6 years; range, 4.6-80.3 years; 64 female [55.2%]), whereas 14 (10.8%) had craniofacial FD that did not involve the temporal bone. Of the 183 ears with temporal bone FD, hearing loss was identified in 41 ears (22.4%) and was conductive in 27 (65.9%), sensorineural in 12 (29.3%), and mixed in 2 (4.9%). Hearing loss was mild and nonprogressive in most participants. Whereas EACs were narrower in ears with FD (mean difference [MD], 0.33 mm; 95% CI, 0.11-0.55 mm), this finding was associated with conductive hearing loss in only 4 participants. Fibrous dysplasia crowding of the ossicles was associated with conductive hearing loss (odds ratio [OR], 5.0; 95% CI, 2.1-11.6). The IAC length was not different between ears with and without FD (MD, -0.37; 95% CI, -0.95 to 0.211); however, canals were elongated in ears with sensorineural hearing loss (MD, -1.33; 95% CI, -2.60 to -0.07). Otic capsule involvement was noted in only 4 participants, 2 of whom had sensorineural hearing loss. Both MAS-associated growth hormone excess (OR, 3.1; 95% CI, 1.3-7.5) and neonatal hypercortisolism (OR, 11; 95% CI, 2.5-55) were associated with an increased risk of hearing loss . Conclusions and Relevance: Hearing loss in craniofacial FD is common and mild to moderate in most individuals. It typically arises from FD crowding of the ossicular chain and elongation of the IAC, whereas EAC stenosis and otic capsule invasion are less common causes. Individuals with craniofacial FD should undergo otolaryngologic evaluation and monitoring, including assessment to identify those with high-risk features.

A novel auditory ossicles membrane and the development of conductive hearing loss in Dmp1-null mice.

Genetic mouse models are widely used for understanding human diseases but we know much less about the anatomical structure of the auditory ossicles in the mouse than we do about human ossicles. Furthermore, current studies have mainly focused on disease conditions such as osteomalacia and rickets in patients with hypophosphatemia rickets, although the reason that these patients develop late-onset hearing loss is unknown. In this study, we first analyzed Dmp1 lac Z knock-in auditory ossicles (in which the blue reporter is used to trace DMP1 expression in osteocytes) using X-gal staining and discovered a novel bony membrane surrounding the mouse malleus. This finding was further confirmed by 3-D micro-CT, X-ray, and alizarin red stained images. We speculate that this unique structure amplifies and facilitates sound wave transmissions in two ways: increasing the contact surface between the eardrum and malleus and accelerating the sound transmission due to its mineral content. Next, we documented a progressive deterioration in the Dmp1-null auditory ossicle structures using multiple imaging techniques. The auditory brainstem response test demonstrated a conductive hearing loss in the adult Dmp1-null mice. This finding may help to explain in part why patients with DMP1 mutations develop late-onset hearing loss, and supports the critical role of DMP1 in maintaining the integrity of the auditory ossicles and its bony membrane.

Risk of progressive hearing loss in untreated superior semicircular canal dehiscence.

OBJECTIVE: Patients with incidental or minimally symptomatic superior semicircular canal dehiscence (SSCD) are usually observed, without surgical repair. However, it remains unknown whether a labyrinthine fistula of the superior semicircular canal is associated with progressive conductive or sensorineural hearing loss over time. STUDY DESIGN: Retrospective review at two tertiary care academic referral centers. METHODS: Adults analyzed were diagnosed with SSCD by high-resolution temporal bone computed tomography and vestibular evoked myogenic potential testing and observed with a minimum of two sequential audiograms. Patients with other potential causes of hearing impairment were excluded. RESULTS: A total of 40 ears in 30 adult patients (median age: 59 years; 63% female) were analyzed. Median audiometric follow-up was 23 months (range 1-136 months). None experienced a sudden hearing loss over the follow-up period. In patients with audiometric follow-up of at least 20 months (median 34 months), the median change in air-conduction pure tone average and air-bone gap was 0.9 decibels (dB) per year (interquartile range [IQR] 0-2.1) and 0.7 dB per year (IQR 0-2.0), respectively. Speech discrimination scores did not differ when comparing median initial (100%) and median final (98%) scores (P = 0.77). There was no statistically significant change in bone-conduction thresholds at 0.5, 1, 2, and 4 kHz over the period of observation. CONCLUSION: The risk of progressive hearing loss with observed SSCD is low during short- and intermediate-term follow-up. Further studies are necessary to determine whether late hearing loss occurs. Such information may be critical toward patient counseling regarding the need for and timing of surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1181-1186, 2017.

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis.

Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

[Analyses of the clinical characteristics of unilateral conductive hearing loss with intact tympanic membrane].

OBJECTIVE: To analyze the clinical characteristics of unilateral conductive hearing loss with intact tympanic membrane, and summarize the key diagnostic points, differential diagnosis and observe the effects of surgical treatment. METHODS: We reviewed data from 82 patients with unilateral conductive hearing loss with intact tympanic membranes who accepted the exploratory tympanotomy from April 2011 to September 2013. There were 41 males and 41 females, aged from 7 to 66( averaged 26.5±13.7)years, with a history of one month to 50 years. The history, clinical symptoms, audiological evaluation, high resolution temporal bone CT, the results of surgical exploration and hearing reconstruction were analyzed. RESULTS: The exploratory tympanotomy revealed 43 cases of congenital middle ear malformations (52.4%), 22 cases of otosclerosis (26.8%), eight cases of congenital cholesteatoma (9.8%), six cases of trauma induced conductive hearing loss (7.3%), three cases of congenital ossicular malformations with congenital cholesteatoma (3.7%). Progressive hearing loss was common in patients with otosclerosis and congenital cholesteatoma, and patients with congenital middle ear malformations described their hearing loss since childhood. High resolution temporal bone CT of congenital middle ear malformation, trauma induced conductive hearing loss, congenital cholesteatoma diagnosis rate was 40.0%, 50.0%, and 83.3% respectively. The preoperative air-conductive threshold of patients with absence of the oval window were increased to (66.9±1.1)dBHL, the preoperative bone-conductive threshold achieved (28.3±10.4)dBHL at 2 000 Hz. While patients with stapes fixation and that with ossicular chain discontinuity were (27.2±9.7)dBHL and (17.8±8.8)dBHL(P=0.000)respectively. Through the tympanic exploration with endaural incision under the microscope, different hearing reconstruction were applied according to different lesions. After the operation, the hearing level of 52 patients with return visit were improved, the mean air-conductive threshold were decreased from (60.0±11.4)dBHL to (32.2±12.1)dBHL(P=0.000); and the mean ABG were decreased from (43.2±12.0)dB to (16.3±9.4)dB(P=0.000). CONCLUSIONS: Congenital middle ear malformations, otosclerosis, congenital cholesteatoma are the most common causes in unilateral conductive hearing loss with an intact tympanic membrane. The diagnosis rate can be improved by analyzing the clinical features. Through exploratory tympanotomy and hearing reconstruction, we can clarify the diagnosis and achieve a satisfying hearing recover.

Guilty as CHARGED: p53's expanding role in disease.

Unrestrained p53 activity during development, as occurs upon loss of the p53 negative regulators Mdm2 or Mdmx, causes early embryonic lethality. Surprisingly, co-expression of wild-type p53 and a transcriptionally-dead variant of p53, with mutations in both transactivation domains (p53(L25Q,W26S,F53Q,F54S)), also causes lethality, but later in gestation and in association with a host of very specific phenotypes reminiscent of a syndrome known as CHARGE. Molecular analyses revealed that wild-type p53 is inappropriately activated in p53(5,26,53,54/)(+) embryos, triggering cell-cycle arrest or apoptosis during development to cause CHARGE phenotypes. In addition, CHARGE syndrome is typically caused by mutations in the CHD7 chromatin remodeler, and we have shown that activated p53 contributes to phenotypes caused by CHD7-deficiency. Together, these studies provide new insight into CHARGE syndrome and expand our understanding of the role of p53 in diseases other than cancer.

Disrupted bone remodeling leads to cochlear overgrowth and hearing loss in a mouse model of fibrous dysplasia.

Normal hearing requires exquisite cooperation between bony and sensorineural structures within the cochlea. For example, the inner ear secretes proteins such as osteoprotegrin (OPG) that can prevent cochlear bone remodeling. Accordingly, diseases that affect bone regulation can also result in hearing loss. Patients with fibrous dysplasia develop trabecular bone overgrowth resulting in hearing loss if the lesions affect the temporal bones. Unfortunately, the mechanisms responsible for this hearing loss, which could be sensorineural and/or conductive, remain unclear. In this study, we used a unique transgenic mouse model of increased Gs G-protein coupled receptor (GPCR) signaling induced by expression of an engineered receptor, Rs1, in osteoblastic cells. These ColI(2.3)+/Rs1+ mice showed dramatic bone lesions that histologically and radiologically resembled fibrous dysplasia. We found that ColI(2.3)+/Rs1+ mice showed progressive and severe conductive hearing loss. Ossicular chain impingement increased with the size and number of dysplastic lesions. While sensorineural structures were unaffected, ColI(2.3)+/Rs1+ cochleae had abnormally high osteoclast activity, together with elevated tartrate resistant acid phosphatase (TRAP) activity and receptor activator of nuclear factor kappa-B ligand (Rankl) mRNA expression. ColI(2.3)+/Rs1+ cochleae also showed decreased expression of Sclerostin (Sost), an antagonist of the Wnt signaling pathway that normally increases bone formation. The osteocyte canalicular networks of ColI(2.3)+/Rs1+ cochleae were disrupted and showed abnormal osteocyte morphology. The osteocytes in the ColI(2.3)+/Rs1+ cochleae showed increased expression of matrix metalloproteinase 13 (MMP-13) and TRAP, both of which can support osteocyte-mediated peri-lacunar remodeling. Thus, while the ossicular chain impingement is sufficient to account for the progressive hearing loss in fibrous dysplasia, the deregulation of bone remodeling extends to the cochlea as well. Our findings suggest that factors regulating bone remodeling, including peri-lacunar remodeling by osteocytes, may be useful targets for treating the bony overgrowths and hearing changes of fibrous dysplasia and other bony pathologies.

Facial nerve schwannomas presenting as occluding external auditory canal masses: a therapeutic dilemma.

OBJECTIVE: To present a series of patients with facial nerve schwannomas (FNSs) presenting as occluding external auditory canal (EAC) masses. STUDY DESIGN: Retrospective case series. PATIENTS: Four patients were identified with mastoid segment FNSs occluding the EAC. Three patients presented with conductive hearing loss (CHL), and the fourth presented with facial paralysis, later developing CHL. INTERVENTION: One patient underwent conservative debulking, removing the EAC component only. Two patients were managed nonoperatively with periodic cleaning of entrapped keratin. The fourth patient received radiation therapy. MAIN OUTCOME MEASURES: Facial nerve function, canal cholesteatoma formation, and hearing. RESULTS: Among the patients managed with serial cleaning of entrapped keratin, one maintained normal facial function and one worsened to House-Brackmann II/VI. Facial function worsened to House-Brackmann II/VI in the patient who underwent surgical debulking. The fourth patient, who received radiation, developed complete facial paralysis. All patients accumulated keratin medial to the tumor, and all had CHL. CONCLUSION: When evaluating an EAC tumor, it is important to obtain imaging before biopsy because biopsy of a schwannoma can result in paralysis. EAC occlusion by a schwannoma presents a challenging management issue, particularly when cholesteatoma forms between the tumor and the tympanic membrane. The primary goal is maintaining normal facial function as long as possible and avoiding secondary ear canal complications. The presence of canal occlusion limits the choice of stereotactic radiation because this leads to a month-long period of tumor swelling and cutaneous sloughing. Resection and grafting are indicated when substantial facial weakness or twitch develops.

Temporal bone changes in patients with Goldenhar syndrome with special emphasis on inner ear abnormalities.

OBJECTIVE: Goldenhar syndrome is a developmental disorder presenting with orofacial and vertebral anomalies, which are also accompanied by abnormalities in other organs. We examined temporal bone changes with special emphasis on inner ear abnormalities in these patients. STUDY DESIGN: A retrospective review of 7 new cases in addition to a previously published series of 14 cases with clinically diagnosed Goldenhar syndrome was carried out to search for inner ear anomalies. In addition, temporal bone imaging studies from the literature were summarized and compared with our results. SETTING: Departments of Neuroradiology and Otorhinolaryngology at a university hospital. PATIENTS: In addition to the previous series of 14 patients, 7 new patients with Goldenhar syndrome were identified. INTERVENTIONS: Patients underwent otologic examination, audiometric studies, and high-resolution computed tomography (CT) or magnetic resonance imaging (MRI) of the temporal bone. MAIN OUTCOME MEASURE: Temporal bone changes and specifically inner ear malformations. RESULTS: Nineteen of 21 patients showed changes of the external and middle ear correlating with the literature. Seven of 21 patients showed inner ear abnormalities constituting one-third of all patients. These ranged from mild such as vestibular enlargement to severe defects such as cochlear hypoplasia and common cavity. CONCLUSION: Inner ear abnormalities were present in one-third of patients. Although in some cases, these might not be of clinical significance, some patients show severe defects of the inner ear requiring more complex hearing loss therapy. Therefore, imaging of the temporal bone structures is important in the care of these patients.

Heptanol application to the mouse round window: a model for studying cochlear lateral wall regeneration.

OBJECTIVE: Identify cells supporting cochlear lateral wall regeneration. STUDY DESIGN: Prospective controlled trial. SETTING: Laboratory. Human presbyacusis occurs, in part, secondary to age-related degeneration of cochlear lateral wall structures such as the stria vascularis and spiral ligament fibrocytes. This degeneration is likely linked to the diminished regenerative capacity of lateral wall cells with age. While lateral wall regeneration is known to occur after an acute insult, this process remains poorly understood and the cells capable of self-replication unidentified. We hypothesized that spiral ligament fibrocytes constitute these proliferative cells. SUBJECTS AND METHODS: To test the hypothesis, an acute ototoxic insult was created in 65 normal-hearing, young adult mice via cochlear exposure to heptanol. Sacrifice occurred at 1 to 60 days posttreatment. Auditory brainstem responses, 5-ethynyl-2'-deoxyuridine assay, and immunostaining were used to assess regeneration. RESULTS: Posttreatment hearing thresholds were elevated in nearly all treated mice. Selective fibrocyte apoptosis and strial injury were observed at the time of peak hearing loss around 1 to 7 days posttreatment. Cellular proliferation was detected in the region of type II fibrocytes during this time. Hearing thresholds plateaued at 7 days posttreatment followed by a significant recovery of both hearing and morphologic appearance. Permanent outer hair cell degeneration was observed. CONCLUSIONS: Heptanol application to the round window of young adult mice is a rapid, selective, and reliable technique for investigating proliferation in the cochlear lateral wall. The data indirectly showed that spiral ligament fibrocytes may be the proliferative cells of the cochlear lateral wall. Further studies of this process are needed.