A mouse model of autoimmune inner ear disease without endolymphatic hydrops.

Autoimmune inner ear disease (AIED) is an organ-specific disease characterized by irreversible, prolonged, and progressive hearing and equilibrium dysfunctions. The primary symptoms of AIED include asymmetric sensorineural hearing loss accompanied by vertigo, aural fullness, and tinnitus. AIED is divided into primary and secondary types. Research has been conducted using animal models of rheumatoid arthritis (RA), a cause of secondary AIED. However, current models are insufficient to accurately analyze vestibular function, and the mechanism underlying the onset of AIED has not yet been fully elucidated. Elucidation of the mechanism of AIED onset is urgently needed to develop effective treatments. In the present study, we analyzed the pathogenesis of vertigo in autoimmune diseases using a mouse model of type II collagen-induced RA. Auditory brain stem response analysis demonstrated that the RA mouse models exhibited hearing loss, which is the primary symptom of AIED. In addition, our vestibulo-oculomotor reflex analysis, which is an excellent vestibular function test, accurately captured vertigo symptoms in the RA mouse models. Moreover, our results revealed that the cause of hearing loss and vestibular dysfunction was not endolymphatic hydrops, but rather structural destruction of the organ of Corti and the lateral semicircular canal ampulla due to an autoimmune reaction against type II collagen. Overall, we were able to establish a mouse model of AIED without endolymphatic hydrops. Our findings will help elucidate the mechanisms of hearing loss and vertigo associated with AIED and facilitate the development of new therapeutic methods.

A Rare Case of Angiofibroma Presenting as an Endolymphatic Sac Tumor.

A 30-year-old man presented with minute-long episodes of vertigo and severe autophony. CVEMP showed a decreased threshold when testing the left side, potentially indicating SSCD. A subsequent MRI demonstrated a multi-lobulated, cystic mass in the temporal bone and the radiological diagnosis at that time was ELST. Tumor excision was performed, and microscopic examination of the excised material revealed fibrovascular tissue without signs of papillary or cystic projections. The conclusion of the histological assessment rendered a diagnosis of angiofibroma. We were unable to find a previous report of ENA originating around the endolymphatic sac. Laryngoscope, 134:1897-1900, 2024.

Third window lesions of the inner ear: A pictorial review.

PURPOSE: Radiographic review of pathologies that associate with third window syndrome. METHODS: Case series and literature review. RESULTS: Eight unique third window conditions are described and illustrated, including superior, lateral, and posterior semicircular canal dehiscence; carotid-cochlear, facial-cochlear, and internal auditory canal-cochlear dehiscence, labyrinthine erosion from endolymphatic sac tumor, and enlarged vestibular aqueduct. CONCLUSION: The present study highlights the characteristic imaging features and symptoms to differentiate third window pathologies for expedient diagnosis and management planning.

The role of the stria vascularis in neglected otologic disease.

The stria vascularis (SV) has been shown to play a critical role in the pathogenesis of many diseases associated with sensorineural hearing loss (SNHL), including age-related hearing loss (ARHL), noise-induced hearing loss (NIHL), hereditary hearing loss (HHL), and drug-induced hearing loss (DIHL), among others. There are a number of other disorders of hearing loss that may be relatively neglected due to being underrecognized, poorly understood, lacking robust diagnostic criteria or effective treatments. A few examples of these diseases include autoimmune inner ear disease (AIED) and/or autoinflammatory inner ear disease (AID), Meniere's disease (MD), sudden sensorineural hearing loss (SSNHL), and cytomegalovirus (CMV)-related hearing loss (CRHL). Although these diseases may often differ in etiology, there have been recent studies that support the involvement of the SV in the pathogenesis of many of these disorders. We strive to highlight a few prominent examples of these frequently neglected otologic diseases and illustrate the relevance of understanding SV composition, structure and function with regards to these disease processes. In this study, we review the physiology of the SV, lay out the importance of these neglected otologic diseases, highlight the current literature regarding the role of the SV in these disorders, and discuss the current strategies, both approved and investigational, for management of these disorders.

Inner ear salivary gland choristoma extending to the middle ear with congenital profound hearing loss and facial palsy: a case report.

BACKGROUND: Salivary gland choristoma (SGCh) is a rare benign tumor reported in several unusual sites, such as the gastrointestinal tract, the optic nerve, and the internal auditory canal, but never reported in the inner ear. CASE PRESENTATION: An 8-year-old girl with a history of left profound congenital hearing loss presented to us with ipsilateral progressive severe facial nerve palsy (House-Brackmann Grade VI). The left tympanic membrane was swollen with a pulsatile tumor. Radiological investigations revealed a multilocular tumor in the inner ear extending into the middle ear and internal auditory canal (IAC). We performed a partial resection of the tumor by transmastoid approach to preserve the anatomical structure of the facial nerve. The tumor was pathologically diagnosed as SGCh. Two years after surgery, her facial function recovered to House-Brackmann Grade II and the residual tumor did not show regrowth on MRI. CONCLUSIONS: Although the natural course of this rare tumor is unknown, a partial resection is an acceptable treatment procedure when functional recovery of the facial nerve is anticipated.

The Pathogenesis of secondary forms of Autoimmune Inner Ear Disease (AIED): advancing beyond the audiogram data.

INTRODUCTION: Autoimmune Inner Ear Disease (AIED) can be of a primary or secondary type. To date, a clear pathogenesis of the disease is still not available. Focusing on the secondary forms of AIED, the aim of this review is to (i) assess and describe the hearing involvement in patients affected by autoimmune diseases, (ii) describe the possible association between clinical features (among serological/laboratory data and disease activity/duration) and hearing impairment, (iii) show evidence connecting the AIED types with various etiopathogenetic mechanisms. AREAS COVERED: A PRISMA-compliant systematic review was performed. Medline, Cochrane, Embase, and Cinahl were searched from 1 January 2015 through to 5 August 2020. Overall, 16 studies (involving 1043 participants) were included in the review. The data in the literature suggested that bilateral mild-to-moderate sensorineural hearing loss is a commonly reported clinical symptom of AIED. EXPERT OPINION: Patients with systemic autoimmune disorders present a cochlear injury which might be associated with the humoral and/or cellular immune response against the inner ear. To date, AIED pathogenesis remains an open issue, due to the rarity of these clinical entities and due to the difficulties in investigating the inner ear immunology, considering the inner ear inaccessibility for tissue sampling.

Evaluation of the Presence of Sensorineural Hearing Loss and the Relationship With Intraoperative Findings in Cholesteatoma.

We investigated whether cholesteatoma is associated with sensorineural hearing loss (SNHL) and the effects of a lateral semicircular canal (LSCC) fistula, destruction of stapes, localization of cholesteatoma, and air-bone gap (ABG) size on SNHL. The charts of 159 patients who had received surgery for unilateral cholesteatoma were examined retrospectively. In all patients, air conduction and bone conduction (BC) thresholds in both ears were measured at 500, 1000, 2000, and 4000 Hz. Differences in BC thresholds between ears with cholesteatoma and contralateral ears were calculated. Demographics, localization of cholesteatoma, presence of LSCC fistula, condition of stapes, and ABG size on the affected ear were evaluated. There were significantly greater BC thresholds in ears with cholesteatoma than in normal ears for each frequency. Comparing the average BC differences at the different cholesteatoma locations, there were significant differences between the tympanic cavity + all mastoid cell group and attic, attic + antrum, and tympanic cavity + antrum groups. The BC differences at 4000 Hz were significantly high in patients with LSCC fistula. There were no significant relationships between the condition of the stapes and BC differences at any frequencies. There were significant correlations between average ABG and BC threshold differences at all frequencies. A significant relationship was found between cholesteatoma and SNHL. Patients with advanced cholesteatoma had significantly higher levels of SNHL. The BC threshold differences increased with increases in the ABG.

Incidence of Inner Ear Disorders in Various Forms of Acute Otitis Media in ENT Practices in Germany.

OBJECTIVE: The aim of this study was to determine the incidence of inner ear involvement in various forms of acute otitis media (AOM) in ear, nose, and throat (ENT) practices in Germany. METHODS: Patients who had been diagnosed with various forms of AOM in the years 2010 to 2017 were enrolled in the study from a nationwide, representative practice database (Disease Analyzer, IQVIA). In these patients, the incidence of simultaneous or subsequent inner ear disorders (IED) was determined within 7 days and within 12 months from the date of an AOM diagnosis. RESULTS: A total of 286 186 patients with AOM were enrolled. The most frequent diagnoses were "nonsuppurative otitis media, unspecified" (47.6%) and "otitis media, unspecified" (39.0%). The diagnoses of hemorrhagic bullous myringitis (BM) or influenza-induced AOM were very rarely found in the database. The highest incidence of IED after 7 days and 12 months was found in "nonsuppurative otitis media, unspecified" (7.7% and 15.9%, respectively), followed by "otitis media, unspecified" (5.6% and 13.5%, respectively). The incidences of the most frequent IED "hearing loss, unspecified" and "sensorineural hearing loss, unspecified" increased proportionally with increasing patient age, while the rare diagnoses of "labyrinthitis" and "ototoxic hearing loss" were evenly distributed among the age groups. CONCLUSION: In ENT practices in Germany, both various forms of AOM, as well as simultaneous or subsequent IED, are mostly being coded in an unspecific way, while specific forms such as hemorrhagic BM, influenza-induced AOM, and labyrinthitis are coded very rarely. Older patients have a higher risk of IED in AOM. A visit due to AOM seems to be a regular occasion for the initial diagnosis of hearing impairment in the elderly individuals. The highest risk of IED was found in nonsuppurative AOM.

Meningiomas of the Internal Auditory Canal.

OBJECTIVE: Identify and define specific preoperative and postoperative characteristics of intracanalicular meningiomas (ICMs) in order to improve their diagnosis and management, and to differentiate them from intrameatal vestibular schwannomas (IMVSs). METHODS: Preoperative symptomatology, magnetic resonance imaging (MRI), and postoperative outcomes of 28 ICMs were analyzed. The results were compared to the literature and IMVSs treated by our group. RESULTS: Anacusis and progressive hearing loss were more frequent in the present population than the cases reviewed (P = .0064 and P = .0001, respectively). Hearing loss affected more than 90% of the patients, with anacusis in 32.1% of the cases. Facial palsy affected 17.9% of the patients. In comparison to IMVSs, preoperative anacusis was more associated to meningiomas (P = .0037), and the facial nerve was more compromised in ICMs than IMVSs, both preoperatively (P = .0011) and at follow-up (P < .0001). According to a re-evaluation of preoperative MRIs and comparison with IMVSs, linear tumor borders, and linear morphology along the internal auditory canal wall, but not the presence of a dural tail, were significantly more present in ICMs (P = .0035, P = .0004, P = .1963, respectively). These characteristics could have led to a correct preoperative diagnosis in 61% of our cases. CONCLUSION: Contrariwise to IMVSs, the frequent preoperative anacusis and facial palsy demonstrate the more aggressive nature of ICMs, which also carry a higher risk of postoperative facial palsy and difficulty to preserve hearing. An attentive evaluation of imaging should ease diagnosis, and asymptomatic or stable ICMs should be enrolled in a wait-and-scan protocol. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E413-E419, 2021.

Phosphatidylinositol 4-kinase ß mutations cause nonsyndromic sensorineural deafness and inner ear malformation.

Congenital hearing loss is a common disorder worldwide. Heterogeneous gene variation accounts for approximately 20-25% of such patients. We investigated a five-generation Chinese family with autosomal-dominant nonsyndromic sensorineural hearing loss (SNHL). No wave was detected in the pure-tone audiometry, and the auditory brainstem response was absent in all patients. Computed tomography of the patients, as well as of two sporadic SNHL cases, showed bilateral inner ear anomaly, cochlear maldevelopment, absence of the osseous spiral lamina, and an enlarged vestibular aqueduct. Such findings were absent in nonaffected persons. We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4KB gene (p.Gln121Arg) encoding phosphatidylinositol 4-kinase ß (PI4KB) from the patients in this family. In addition, 3 missense PI4KB (p.Val434Gly, p.Glu667Lys, and p.Met739Arg) mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases. No such mutations were present within 600 Chinese controls, the 1000 genome project, gnomAD, or similar databases. Depleting pi4kb mRNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment, mimicking the patient phenotypes. Moreover, overexpression of 4 human missense PI4KB mutant mRNAs in zebrafish embryos resulted in impaired hearing function, suggesting dominant-negative effects. Taken together, our results reveal that PI4KB mutations can cause SNHL and inner ear malformation. PI4KB should be included in neonatal deafness screening.

Labyrinthitis and Labyrinthitis Ossificans - A case report and review of the literature.

Labyrinthitis most commonly results from an infectious and less commonly from an inflammatory process of the inner ear, but it can be associated with temporal bone trauma, hemorrhage, or tumor. This inflammation (regardless of the etiology) disrupts the transmission of sensory information from the ear to the brain. Labyrinthitis ossificans is the pathological ossification of the membranous labyrinthine spaces in response to an insult to the inner ear involving membranous labyrinth or the endosteum of the otic capsule. Herein, we present a case of a 67-year-old female with progressive bilateral sensorineural hearing loss and positional vertigo.

Exploratory tympanotomy in sudden sensorineural hearing loss for the identification of a perilymphatic fistula - retrospective analysis and review of the literature.

OBJECTIVE: The diagnostic value of exploratory tympanotomy in sudden sensorineural hearing loss remains controversial. This study and review were performed to identify the incidence of perilymphatic fistula in patients with sudden sensorineural hearing loss. The effectiveness of tympanotomy for sealing of the cochlear windows in cases with perilymphatic fistula was evaluated. METHODS: A search in common databases was performed. Overall, 5034 studies were retrieved. Further, a retrospective analysis on 90 patients was performed. RESULTS: Eight publications dealing with tympanotomy in patients with sudden sensorineural hearing loss were identified. In 90 patients diagnosed with sudden sensorineural hearing loss and undergoing exploratory tympanotomy, 10 patients (11 per cent) were identified with a perilymphatic fistula, and this corresponds to the results obtained from our review (13.6 per cent). CONCLUSION: There was no significant improvement after exploratory tympanotomy and sealing of the membranes for patients with a definite perilymphatic fistula.

Inner-Ear Disorders Presenting with Air-Bone Gaps: A Review.

Air-bone gaps (ABGs) are commonly found in patients with conductive or mixed hearing loss generally due to outer- and/or middle-ear diseases such as otitis externa, tympanic membrane perforation, interruption or fixation of the ossicular chain, and chronic suppurative otitis media. ABGs can also be found in correlation with inner-ear disorders, such as endolymphatic hydrops, enlarged vestibular aqueduct syndrome, semicircular canal dehiscence, gusher syndrome, cochlear dehiscence, and Paget disease's as well cerebral vascular anomalies including dural arteriovenous fistula. The typical clinical presentation of inner-ear conditions or cerebral vascular anomalies causing ABGs includes audiological and vestibular symptoms like vertigo, oscillopsia, dizziness, imbalance, spinning sensation, pulsatile or continuous tinnitus, hyperacusis, autophony, auricular fullness, Tullio's phenomenon, and Hennebert's sign. Establishing a definitive diagnosis of the underlying condition in patients presenting with an ABG is often challenging to do and, in many patients, the condition may remain undefined. Results from an accurate clinical, audiological, and vestibular evaluation can be suggestive for the underlying condition; however, radiological assessment by computed tomography and/or magnetic resonance imaging is mandatory to confirm any diagnostic suspicion. In this review, we describe and discuss the most recent updates available regarding the clinical presentation and diagnostic workup of inner-ear conditions that may present together with ABGs.

Use of topical fluorescein in the diagnosis and localization of perilymphatic fistula.

OBJECTIVE: The purpose of this video presentation is to demonstrate the effect of intraoperative dilute topical fluorescein in perilympatic fistula diagnosis and localization. MATERIALS AND METHODS: Explorative tympanotomy was performed for the diagnosis, localization and repair of the fistula in the patient who had a pre-diagnosis of perilymphatic fistula. Topical fluorescein was applied intraoperatively to localize the defect. RESULT: A clear change of color was distinguished from yellow to green leading to diagnosis of the perilymphatic fistula and also showed the origin of the fistula. CONCLUSION: Topical application of dilute fluorescein is a convenient and effective tool in the diagnosis and localization of perilymphatic fistula.

Rare otologic presentation of cat eye syndrome.

We encountered an extremely rare case where a patient with cat eye syndrome (CES) who presented with symptoms of posterior semicircular canal dehiscence (PSCD). CES is a rare genetic disorder, resulting from duplication of chromosome 22. Patients may present with variable phenotypes, including characteristic of coloboma, heart defect, periauricular skin pit/tag, microtia, anal atresia and mildly retarded mental development in some cases. PSCD is also a disease of the inner ear, where patients present with third window signs and symptoms due to lack of bony coverage. PSCD is usually associated with a high riding jugular bulb and fibrous dysplasia. In this study, we report a new otologic finding in CES patient as an association of PSCD and high jugular pulp. We describe the work up and its findings and the management of this patient. SIMILAR CASES PUBLISHED:: None.

Superior semicircular canal dehiscence postoperative outcomes: A case series of 156 repairs.

Previous studies have looked at differences in predisposing factors, symptomology, treatment options, and outcomes in patients with SSCD experiencing audiologic and vestibular symptoms, however this study utilizes data from the largest series of SSCD patients by a single pair of neurosurgeon and head and neck surgeon to date. The objective was to determine what pre-operative factors, if any, contribute to post-operative outcomes in SSCD patients. A retrospective chart review collected patient demographics, preoperative symptoms, and postoperative symptoms. Nonparametric tests were run using IBM® SPSS® Statistics. Fisher's Exact Tests, Spearman's rho, and McNemar's test for paired comparison of binary measures were performed, with a significance level of P < 0.05. A total of 156 SSCD surgeries were performed within a cohort of 119 patients. The majority of patients were female (n = 75, 63.0%). The median age was 55 years (±12.7 years) and median follow-up length was 0.46 months (range: 0.03-59.5 months). Increased postoperative dizziness and hearing loss was significantly correlated with females (P = .048, P = .041). Additionally, males reported significantly improved postoperative hearing (P = .044) with confirmatory audiometry. Serum ionized calcium levels inversely correlated with age using spearman's coefficient (rs = -.260 P = .037). Postsurgical autophony was significantly associated with bilateral SSCD (P = .01). In conclusion, differences in outcomes between patients may have to do with bilateralism of SSCD or gender effects. Proposed theories concerning a "two hit" hypothesis and about calcium feedback regulation in SSCD may play a role in these findings. Understanding differences between symptomology will help facilitate discussions with future patients.

Posterior semicircular canal dehiscence: a diagnostic and surgical conundrum.

Third window defects have increasingly been identified as a cause of vertigo. These defects are bony dehiscences that occur in the bony labyrinth, resulting in abnormal pressure gradient in the inner ear fluids leading to sound (Tullio's phenomenon) or pressure (Hennebert's sign) induced vertigo. The superior semicircular canal dehiscence syndrome is a well-described entity in this regard, however defects of the posterior semicircular canal are rare and may have overlapping symptomatology. We describe the history, clinical profile and management of a patient who had importunate symptoms despite being on conservative management for a year and had resolution of vestibular symptoms following surgical management.

Characteristics of positional nystagmus in patients with horizontal canal canalolithiasis or cupulopathy.

OBJECTIVES: Positional nystagmus can be related to various kinds of disorders. The current study aims to compare the direction-changing horizontal positional nystagmus (DCPN) characteristics in horizontal canal canalolithiasis (HC-canalolithiasis), heavy cupula of the horizontal canal (HC-Hcu), and light cupula of the horizontal canal (HC-Lcu), especially the temporal patterns of positional nystagmus in three disorders. METHODS: 52 patients (22 males, 30 females; mean age, 49.6 years) presenting with geotropic or apogeotropic DCPN were enrolled, and they were divided into HC-canalolithiasis, HC-Hcu, or HC-Lcu groups according their nystagmus characteristics. We compared their latency, time constant, peak slow-phase velocity (SPV), time to reach peak SPV intensity (Tpeak), and time to decay to half-peak intensity (T1/2peak). RESULTS: The time to reach peak SPV did not differ significantly between the HC-Hcu (23.1 ± 8.6 s) and HC-Lcu (24.4 ± 9.9 s) groups (p = 0.733), but was significantly longer than that of the HC-canalolithiasis group (5.4 ± 3.5 s; p ≤ 0.001). The peak intensity did not differ among the canalolithiasis (36.4 ± 20.6º/s), HC-Hcu (30.1 ± 23.6º/s), and HC-Lcu (21.4 ± 12.7º/s) groups (p = 0.133). The onset latency also had no statistical difference among three groups (p = 0.200). The nystagmus patterns of HC-Lcu and HC-Hcu groups were similar, including latency, peak SPV intensity, Tpeak, T1/2peak, and SPV in 20 s, 40 s, 60 s, 80 s. CONCLUSIONS: The nystagmus characteristics of HC-Hcu and HC-Lcu are similar, except for the fact that movement was in opposite directions, suggesting that HC-Hcu and HC-Lcu may result from a similar pathophysiological mechanism (cupulopathy) differing from that underlying canalolithiasis.