Dynamic Molecular Markers of Otosclerosis in the Human Cochlea.

OBJECTIVE: To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the pathogenesis of otosclerosis. METHODS: Archival celloidin formalin-fixed 20-micron thick histologic sections from 7 patients diagnosed with otosclerosis were studied and compared to controls. Sections in the mid-modiolar region were immunoreacted with rabbit polyclonal antibodies against nidogen-1, ß2-laminin, collagen-IX, BSP, and monoclonal antibodies against TGF ß-1 and ubiquitin. Digital images were acquired using a high-resolution light and laser confocal microscope. RESULTS: Nidogen-1, BSP, and collagen-IX were expressed in the otospongiotic regions, and to lesser extent, in the otosclerotic regions, the latter previously believed to be inactive. ß2-laminin and ubiquitin were uniformly expressed in both otospongiotic and otosclerotic regions. There was a basal level of expression of all of these markers in the normal hearing and sensorineural hearing loss specimens utilized as control. TGF ß -1, however, though present in the otosclerosis bones, was absent in the normal hearing and sensorineural hearing loss controls. CONCLUSIONS: Our results propose that the activity and function of TGF-1 may play a key role in the development and pathogenesis of otosclerosis. Further studies utilizing a higher number of temporal bone specimens will be helpful for future analysis and to help decipher its role as a potential target in therapeutic interventions.

Otosclerosis under the magnifying glass.

Otosclerosis is a bone condition affecting the stapes bone within the otic capsule, and its exact cause is still unknown. It is characterized by a lack of proper remodeling of newly formed vascular and woven bone, leading to the development of abnormal osteons and the formation of sclerotic bone. Bilateral otosclerosis is seen in 80% of patients and 60% of otosclerosis patients have a family history of the condition. The etiology of this disease is still unknown, there are lots of theories to explain it. The histopathological (HP) studies of otosclerosis showed that osteoblasts, osteoclasts, vascular proliferation, fibroblasts, and histiocytes were observed in the stapes footplate. The onset of the symptoms occurs by the early third decade of life, usually it doesn't start later. In otosclerosis, the energy exerted by sound at the level of the tympanic membrane is reduced in the inner ear due to the fixation and rigidity of the ossicular chain, leading to hearing loss, especially for low frequencies. The primary clinical symptom of otosclerosis is conductive hearing loss but it is important to note that sensorineural hearing loss and mixed hearing loss can also occur as secondary symptoms of the condition. Another symptom present in patients with otosclerosis is tinnitus. The paper carried out a retrospective study of 70 patients diagnosed with otosclerosis in the Department of Otorhinolaryngology of Emergency City Hospital, Timisoara, Romania, between January 2021 to December 2022. Tissue fragments were processed at Service of Pathology by standard Hematoxylin-Eosin staining. The HP diagnosis was completed using Masson's trichrome staining, Giemsa histochemical staining, and immunohistochemical (IHC) reactions with anti-cluster of differentiation (CD)20, anti-CD3, anti-CD4, anti-CD8, anti-CD34, and anti-CD31 antibodies. The microscopic examination showed a chronic diffuse inflammatory infiltrate that consisted predominantly of mature T-lymphocytes, immunohistochemically positive for CD3, CD4 and CD8. There were also present rare CD20-positive B-lymphocytes. Among the lymphocytes, relatively numerous mast cells were identified, highlighted histochemically by the Giemsa staining. They had numerous purple-violet intracytoplasmic granules. In the connective tissue support, a relatively rich vascular network was identified, consisting of hyperemic capillaries, highlighted immunohistochemically with anti-CD31 and anti-CD34 antibodies. Bone tissues trabeculae showed extensive areas of fibrosis. The collagen fibers were highlighted by Masson's trichrome staining, being stained in green, blue, or bluish green.

Genetic variants and altered expression of SERPINF1 confer disease susceptibility in patients with otosclerosis.

Otosclerosis (OTSC) is a focal and diffuse bone disorder of the human middle ear characterized by abnormal bone growth and deposition at the stapes' footplate. This hinders the transmission of acoustic waves to the inner ear leading to subsequent conductive hearing loss. The plausible convections for the disease are genetic and environmental factors with yet an unraveled root cause. Recently, exome sequencing of European individuals with OTSC revealed rare pathogenic variants in the Serpin Peptidase Inhibitor, Clade F (SERPINF1) gene. Here, we sought to investigate the causal variants of SERPINF1 in the Indian population. The gene and protein expression was also evaluated in otosclerotic stapes to ameliorate our understanding of the potential effect of this gene in OTSC. A total of 230 OTSC patients and 230 healthy controls were genotyped by single-strand conformational polymorphism and Sanger sequencing methods. By comparing the case controls, we identified five rare variants (c.72 C > T, c.151 G > A, c.242 C > G, c.823 A > T, and c.826 T > A) only in patients. Four variants c.390 T > C (p = 0.048), c.440-39 C > T (p = 0.007), c.643 + 9 G > A (p = 0.035), and c.643 + 82 T > C (p = 0.005) were found to be significantly associated with the disease. Down-regulation of SERPINF1 transcript level in otosclerotic stapes was quantified by qRT-PCR, ddPCR and further validated by in situ hybridization. Similarly, reduced protein expression was observed by immunohistochemistry and immunofluorescence in otosclerotic stapes that corroborate with immunoblotting of patients' plasma samples. Our findings identified that SERPINF1 variants are associated with the disease. Furthermore, reduced expression of SERPINF1 in otosclerotic stapes might contribute to OTSC pathophysiology.

Impact of Otosclerosis on Auditory Ossicle Remodeling: A Scanning Electron Microscopy Analysis of Stapes Head Overloads.

BACKGROUND Otosclerosis is a pathology that interferes with the conduction of vibrations to the inner ear, triggering changes in the auditory ossicles and their associated joints due to mechanical overload. This study primarily aims to evaluate these overload-induced modifications in the stapes head resulting from the immobilization of the base of the third auditory ossicle in otosclerosis patients. MATERIAL AND METHODS We conducted a comparative analysis of patients undergoing their first surgery for otosclerosis. The test group consisted of 31 patients who underwent stapedotomy between 2020-2021. For comparison, we utilized a control group comprising stapes samples extracted during vestibular schwannoma surgeries via a transcochlear approach. A prospective analysis of bone tissue surface topography and chemical composition was executed using scanning electron microscopy (SEM). RESULTS SEM analysis of the stapes head in otosclerosis patients relative to the control group displayed no significant differences in chemical composition or the presence of otosclerotic foci. Nonetheless, various forms of bone tissue surface damage were noted on the stapes head in all otosclerosis patients. Mild changes were evident in 90% of the samples, while small linear bone tissue fractures were observed in 58% of the samples. Furthermore, minor osteophytic changes were detected in 16% of the samples. CONCLUSIONS The immobilization of the stapes base by otosclerotic foci instigates overloads in the incus-stapes joint, leading to the eventual remodeling of the stapes head articular surface.

Cellular voids in the pathogenesis of otosclerosis.

BACKGROUND: Otosclerosis is a common ear disease that causes fixation of the stapes and conductive hearing impairment. However, the pathogenesis of otosclerosis is still unknown. Otosclerosis could be associated with the unique bony environment found in the otic capsule. Normal bone remodelling is almost completely absent around the inner ear after birth allowing degenerative changes and dead osteocytes to accumulate. High levels of inner ear anti resorptive osteoprotegerin (OPG) is most likely responsible for this capsular configuration. Studies have demonstrated how osteocyte lifespan variation creates occasional clusters of dead osteocytes, so-called cellular voids, at otosclerotic predilection sites in the human otic capsule. These cellular voids have been suggested as possible starting points of otosclerosis. AIM: To describe the cellular viability in otosclerotic lesions and compare it to that of cellular voids. MATERIALS AND METHODS: The study was based on unbiased stereological quantifications in undecalcified human temporal bones with otosclerosis. RESULTS: Osteocyte viability was found to vary within the otosclerotic lesions. Furthermore, the results presented here illustrate that inactive otosclerotic lesions consist of mainly dead interstitial bone, much like cellular voids. CONCLUSIONS AND SIGNIFICANCE: Focal degeneration in the otic capsule may play an important role in the pathogenesis of otosclerosis.

The Spatial Distribution of Cellular Voids in the Human Otic Capsule: An Unbiased Quantification of Osteocyte-Depleted Areas.

OBJECTIVE: This study aimed to describe the spatial distribution of osteocyte-depleted areas, so-called cellular voids, in the human otic capsule and compare it with that of otosclerosis. BACKGROUND: Systematic histological studies of the bony otic capsule have revealed an osteoprotegerin (OPG)-mediated inhibition of normal bone remodeling around the inner ear. The resulting accumulation of bony degeneration and dead osteocytes has been thoroughly documented, and the spatial distribution of dead osteocytes and matrix microcracks resembles that of the human ear disease otosclerosis. Clusters of dead osteocytes that may interfere with osteocyte connectivity and thereby the OPG signaling pathway have been described in human temporal bones. It is possible that these cellular voids create disruptions in the antiresorptive OPG signal that may give rise to local pathological remodeling. METHODS: Recently, a method of detecting cellular voids was developed. This study uses unbiased stereology to document the spatial distribution of cellular voids in bulk-stained undecalcified human temporal bone. RESULTS: Cellular voids accumulate around the inner ear and increase in number and size with age. Furthermore, cellular voids are more frequently found in the anterior and lateral regions of the otic capsule, which are known predilection sites of otosclerosis. CONCLUSION: This colocalization of cellular voids and otosclerosis suggests a causal relationship between focal degeneration and otosclerotic remodeling.

Computed Tomography Density as a Bio-marker for Histologic Grade of Otosclerosis: A Human Temporal Bone Pathology Study.

HYPOTHESIS: Computed tomography (CT) density measurement can be used to objectively distinguish otosclerosis from normal bone and to determine histologic grades of otosclerosis. BACKGROUND: Otosclerosis can be seen on CT as subtle radiolucent areas. An objective radiologic measurement that corresponds to known otosclerosis pathology may improve diagnostic accuracy, and could be used as a radiologic biomarker for otosclerosis grade. METHODS: A blinded, randomized evaluation of both histologic grade on histopathology slides and CT density measurement was performed on 78 human temporal bone specimens (31 with otosclerosis and 47 controls) that had undergone high-resolution multi-detector CT before histologic processing. Assessments were performed at 11 regions of interest (ROIs) in the otic capsule for each specimen. RESULTS: The CT density measurement mean (Hounsfield Units) ± standard deviation for all ROIs (Nos. 1-9) was 2245 ± 854 for grade 0 (no otosclerosis, n = 711), 1896 ± 317 for grade 1 (inactive otosclerosis, n = 109), and 1632 ± 255 for grades 2 and 3 combined (mixed/active otosclerosis, n 35). There was a strong inverse correlation of CT density to histologic grade at ROIs Nos. 1-5 (ANOVA, p < 0.0001). The inter-rater reliability for CT density was very good (correlation coefficient 0.87, p < 0.05). ROC curves suggested a cut-off of 2,150HU to distinguish otosclerosis from normal bone, and 1,811HU to distinguish low grade from mixed/high grade otosclerosis. CONCLUSIONS: In human temporal bone specimens, CT density may be used to distinguish normal bone from bone involved by otosclerosis. A higher histologic grade (i.e., indicating a more active otosclerotic focus) correlated with lower density.

Relationship between short-term and mid-term hearing outcomes after stapedotomy in patients with otosclerosis: an investigation.

BACKGROUND: Although stapedotomy is effective for patients with clinical otosclerosis, the time of hearing stabilization has not yet been consistent. OBJECTIVE: To investigate the relationships between post-operative follow-up times, hearing outcomes, and threshold shift after stapedotomy. MATERIALS AND METHODS: Fifty-five patients with clinical otosclerosis that underwent stapedotomy were retrospectively studied. Pure tone audiometry tests were conducted within the first month (short-term) and within 1 year (mid-term) postoperatively. Data were analyzed for two rounds of audiometry tests at different postoperative follow-up times. RESULTS: Air conduction (AC) and bone conduction (BC) were significantly correlated with preoperative hearing levels (p<.01). AC, BC, and air bone gap (ABG) significantly improved at the short-term (p<.001) and continued to improve at the mid-term (p<.01). The success rate of surgery increased from 87% at short-term to 98% at mid-term. Less than 1/3 of cases encountered BC deterioration at short-term, whereas most improved at mid-term. CONCLUSIONS: Hearing results showed a trend of improvement between short-term and mid-term follow-ups after stapedotomy. AC, ABG, and success rate displayed significant improvement several months postoperatively. BC deterioration occurred in less than 30% of patients at short-term. The recovery of BC at 4 kHz was later than that of low frequencies.

Distribution of microcrack surface density in the human otic capsule.

BACKGROUND: The bony otic capsule is comprised of highly mineralized and dense compact bone. It is rarely remodelled and degenerative changes, therefore, accumulate around the inner ear. It is also a predilection site for the pathological remodelling seen in otosclerosis. Morphometric studies have documented increased numbers of dead osteocytes and microcracks in the human otic capsule. Microcracks may disrupt the lacuno-canalicular network and cause osteocyte apoptosis ultimately breaking up the perilabyrinthine bone signalling pathways and dynamics. This may be important to understand the pathogenesis of remodelling diseases like otosclerosis. AIMS/OBJECTIVES: This study describes the spatial and regional distribution of microcrack surface density in relation to the inner ear and compares it to that previously recorded for otosclerosis. MATERIAL AND METHODS: Forty-two temporal bones and five ribs were used. All samples were undecalcified, bulk stained in basic fuchsin and plastic embedded. Unbiased stereology was used to estimate the true surface density of microcracks (mm2/mm3) in perilabyrinthine bone. RESULTS: The surface density of microcracks accumulates around the inner ear spaces, particularly in the lateral window regions, and increases with age. CONCLUSIONS AND SIGNIFICANCE: This study documents the spatial and temporal association between microfractures and otosclerosis in the otic capsule.

The Stapes in Otosclerosis: Osteoarthritis of an Ear Ossicle.

Otosclerosis is a pagetoid proliferation of bone remodeling, vascular proliferation, bone resorption and new bone formation in the tympanic region of the temporal bone. The resulting anklyosis of the stapes footplate as it articulates with the oval window is the most common cause of conductive hearing loss in young to middle aged, predominantly Caucasian individuals. The characteristic histologic features have been well documented by autopsy studies of the temporal bone. Although stapedectomy is the surgical treatment for otosclerosis, the stapes specimen may be submitted for gross examination only or not examined at all. A retrospective study of 73 stapedectomy specimens (2008-2019) not including the stapes footplate. Clinical features from the electronic medical record as well as standard histologic sections from surgical specimens were reviewed. Neither the stapedal head nor crura showed histologic features of otosclerosis. There was mild osteoarthritis affecting the head, possibly as a consequence of persistent ossicular vibration superimposed on the ankylosed rigidity. The most common changes were surface fissuring (65%), cartilaginous erosion (49%) and irregularity of the osteochondral interface (51%). An occasional osteophyte (8%) was observed. The ear ossicles, embryologically analogous to long bones of the extremities, develop via endochondral ossification and exhibit articular surfaces of hyaline cartilage. The present observations suggest that a consequence of otosclerotic ankylosis is osteoarthritis of the stapedal head. In this study, the histological features could not be correlated with the severity of hearing loss or duration of clinical disease.

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.

Microcrack surface density in the human otic capsule: An unbiased stereological quantification.

Bone is continuously remodeled to repair and strengthen degenerative bone with accumulating dead osteocytes and microfractures. Inner ear osteoprotegerin (OPG)-mediated inhibition of otic capsular bone remodeling causes excessive perilabyrinthine bone degeneration. Consequently, microcracks accumulate around the inner ear. Microcracks cause osteocyte apoptosis and may disrupt the canalicular network connecting osteocytes. Despite their linear microscopic appearance, microcracks are three-dimensional disruption planes and represent surface areas inside a tissue space. With an elevated microcrack burden the number of disconnected osteocytes is expected to increase. This may prove relevant to ongoing research in otic focal pathologies like otosclerosis. Therefore, an unbiased quantification of the microcrack surface density (mm2 /mm3 ) in the human otic capsule is essential. In this study unbiased stereology was applied to undecalcified bulk stained human temporal bones to demonstrate its feasibility in describing the three-dimensional reality behind two dimensional observations of microcracks. A total of 28 human temporal bones and five ribs were bulk stained in basic fuchsin, serially sectioned and hand-ground to a thickness of 80-120 µm. Both horizontal and vertical sections were produced and compared. This study showed that surface density of microcracks was significantly higher around the inner ear compared to ribs. Furthermore, no significant difference in microcrack surface density between horizontal and vertical sections in the temporal bone was demonstrated.

Measurement of stapes footplate thickness in otosclerosis by ultra-high-resolution computed tomography.

BACKGROUND: Ultra-high-resolution computed tomography (U-HRCT) utilizes a 1024 × 1024 matrix with 0.25-mm section thickness, offering better spatial resolution than conventional multi-detector row CT to detect anatomic data for otologic surgery. AIMS: We examined stapes footplate thickness using U-HRCT in relation to stapedotomy to predict the difficulty of the surgical procedure. MATERIALS AND METHODS: Subjects were 12 otosclerosis patients and 25 controls who underwent diagnostic U-HRCT. A profile curve (Hounsfield units) was used to measure stapes footplate thickness along a perpendicular line across the stapes footplate in a plane parallel to the lateral semicircular canal. RESULTS: Footplate thickness was smaller at the midpoint than just before the anterior crus and just after the posterior crus. Interobserver variability was lowest at the midpoint, where foot plate thickness was significantly greater in the affected ear in otosclerosis patients compared with controls (0.60 ± 0.09 mm vs 0.46 ± 0.04 mm; p < .001). Otosclerosis patients were detected using U-HRCT with a high area under the curve. Difficulty in the stapes opening procedure correlated with stapes footplate thickness. CONCLUSIONS: Footplate thickness on U-HRCT correlated with temporal bone anatomy and corresponded to surgical difficulty. Significance: U-HRCT-derived anatomic data is useful for evaluating the stapes.

Microdrill stapedotomy for otosclerosis with small and large preoperative air-bone gap: a retrospective comparison of results.

Background: In otosclerosis mixed hearing loss is the most frequent symptom and arises when the focus involves the stapes footplate. Surgeons usually prefer to wait a minimum air-bone gap of 25 - 35 dB before surgery.Objectives: To evaluate the outcome of microdrill stapedotomy for otosclerosis in patients with a preoperative air-bone gap (ABG) <25 dB versus patients with a preoperative gap ≥ 25 dB.Material and methods: For this retrospective study, the outcomes and complications after microdrill stapedotomy were compared between adult patients with a preoperative small ABG (n = 127, ABG <25 dB) and those with a large ABG (n = 254, ABG ≥25 dB).Results: The postoperative ABG was significantly smaller than the preoperative ABG (p < .05) in both groups; there were no differences in complications rates (severe sensorineural hearing loss, footplate fracture or early postoperative vertigo) between the two groups.Conclusions: Our findings show that microdrill stapedotomy is safe and can be performed even in patients with a preoperative small ABG without increasing the risk of sensorineural hearing loss due to inner ear damage.

Histopathologic Characteristics of Internal Auditory Canal Diverticula.

HYPOTHESIS: We hypothesize that internal auditory canal (IAC) diverticula occur independent of otosclerosis as demonstrated by temporal bone histopathology. BACKGROUND: Diverticula at the anterior-inferior aspect of the IAC have been described histologically in the setting of cavitary otosclerosis. Recent radiographic studies show the prevalence of IAC diverticula that is higher than what can be accounted for by cavitary otosclerosis alone. METHODS: We examined hematoxylin and eosin temporal bone histopathology slides with otosclerosis involving the IAC. We also examined bones from normal hearing subjects with normal histologic findings. Temporal bones were included if donors were more than 18 years of age at time of death and adequate horizontal cuts were available to evaluate the area of interest. RESULTS: IAC diverticula were found in 33 of 47 (70%) temporal bones with IAC otosclerosis and in 5 of 20 (25%) normal temporal bones. The difference in mean pure tone averages (PTA) in the normal temporal bones with (PTA 7.3 ±â€Š7) and without (PTA 8 ±â€Š2) diverticula was not statistically significant (p = 0.86). CONCLUSION: IAC diverticula which have been previously demonstrated to occur in the setting of cavitary otosclerosis can also occur independent from otosclerosis. Subjects with diverticula but without other temporal bone pathology have normal hearing thresholds.

High-Resolution Computed Tomography of the Inner Ear: Effect of Otosclerosis on Cochlear Aqueduct Dimensions.

OBJECTIVES: The cochlear aqueduct is a bony duct connecting the scala tympani with the subarachnoid space. Given the pathophysiology of otosclerosis, including bone resorption and new bone deposition, we hypothesize that the cochlear aqueduct in otosclerotic ears is narrowed. METHODS: A retrospective review of patients with otosclerosis who have undergone high-resolution computed tomography (HRCT) of the temporal bone was completed. The control cohort included 20 patients with the diagnosis of noise-induced hearing loss, without the diagnosis of otosclerosis. Uniform measurements of cochlear aqueduct dimensions were performed using the axial plane. RESULTS: The otosclerosis cohort included 25 males and 52 females with mean age of 52.2 ± 17.6 years. The control group included 10 males and 10 females with mean age of 64.0 ± 18.5 years. The mean cochlear aqueduct length, width mid canal, aperture base, aperture widest diameter, and funnel diameter in millimeters were 12.19 ± 1.66, 0.68 ± 0.28, 4.21 ± 1.67, 3.23 ± 1.47, and 2.70 ± 1.05 in the ears with otosclerotic foci and 11.57 ± 1.66, 0.69 ± 0.29, 2.56 ± 1.59, 2.77 ± 1.67, and 2.58 ± 1.03 in control group, respectively. Statistical difference was seen in length of cochlear aqueduct, aperture base, and aperture widest diameters (P = .017, <.001, .007). CONCLUSIONS: The length of the cochlear aqueduct and the funnel width are statistically longer in the otosclerotic population compared to control. The width of the cochlear aqueduct is not statistically different.

Clinical Features of Ears With Otosclerosis and Endolymphatic Hydrops.

OBJECTIVE: Endolymphatic hydrops (EH) has been reported in ears with otosclerosis. The objective of this study was to investigate the clinical features of ears with otosclerosis and EH on magnetic resonance imaging (MRI) and identify predictors for the presence of EH. STUDY DESIGN: Retrospective study. SETTING: University hospital. MATERIALS AND METHODS: Forty-six ears from 37 patients with otosclerosis were included in the present study. INTERVENTIONS: The subjects were divided into three groups, those with no, mild, or significant EH, based on 3-T MRI with intravenous injection of gadolinium. Hearing levels and the extent of otosclerotic lesions graded based on the computed tomography (CT) findings were compared among the groups. Moreover, to examine the vascular activity of the disease, intraoperative measurements of blood flow were also evaluated. MAIN OUTCOME MEASURES: Imaging, hearing levels, and blood flow values. RESULTS: The overall rate of EH was 58.7% (27 of 46 ears); cochlear EH (52.2%) was more frequent than vestibular EH (26.1%). Average thresholds in ears with significant EH were significantly higher at several frequencies, both on air and bone conduction, than those with no or mild EH. Significant EH was more frequently observed in ears with advanced stages on CT than in those without advanced stages. The values of blood flow in the area anterior to the oval window were higher in some ears with EH than in ears without EH. CONCLUSION: EH was frequently present in ears with otosclerosis, especially those with severe hearing loss or advanced disease on CT.

Otosclerosis: anatomical distribution of otosclerotic loci analyzed by high-resolution computed tomography.

PURPOSE: To clarify the anatomical distribution of otosclerotic loci in otosclerosis. METHODS: Ninety-five patients with surgically confirmed uni- or bilateral otosclerosis were enrolled into the study. Hypodense areas observed in the otic capsule by high-resolution computed tomography (HRCT) were defined as otosclerotic loci. The location and number of lesions were examined, and the probability of lesion overlap and correlation with age/hearing parameters (air and bone conduction threshold, air-bone gaps) were tested. RESULTS: Otosclerotic loci were confirmed by HRCT in 77 out of 115 operated ears. The three commonly affected sites were the anterior part of the oval window (ant-OW), anterior part of the internal auditory canal (ant-IAC), and pericochlear area (PCochA), with lesions detected in 96.1%, 46.8%, and 26.0% of ears, respectively. Only the ant-OW area was affected in 48.1% of the ears; the ant-IAC in 3.9%; and PCochA in none with significant differences (p < 0.01). The ant-OW lesions preferentially overlapped with ant-IAC (44.6%) than PCochA lesions (27.0%) (p < 0.05). Among double sites diseases, triple sites diseases occurred more commonly in the ant-OW + PCochA group (80%) than ant-OW + ant-IAC group (48.5%) (p < 0.05). There was no correlation between a number of lesions and age/hearing parameters. CONCLUSIONS: Based on the probability of lesion overlap, otosclerotic lesions may initiate at ant-OW followed by ant-IAC and later PCochA. Although the number of lesions showed no immediate correlation with hearing level or age, anatomical stage of the disease estimated by the location and the number of otosclerotic loci could be useful in predicting the future hearing status.

Involvement of the Internal Auditory Canal in Subjects With Cochlear Otosclerosis: A Less Acknowledged Third Window That Affects Surgical Outcome.

OBJECTIVE: To investigate the effects of cavitating lesions involving the internal auditory canal (IAC) in subjects with cochlear otosclerosis with regard to poststapedotomy hearing outcome. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A retrospective chart review of 134 subjects with otosclerosis treated from January 2011 to June 2017 at Seoul National University Bundang Hospital was conducted. Sixteen subjects (23 ears) with temporal bone computed tomography (TBCT)-confirmed cochlear otosclerosis who underwent stapedotomy were included in the study. MAIN OUTCOME MEASURES: Pure tone audiometry (PTA) (i.e., air and bone conduction; AC and BC, respectively) thresholds and air-bone gap (ABG), measured at 6 months postoperatively were compared between cochlear otosclerosis with and without IAC involvement (IAC group and non-IAC group, respectively). RESULTS: A total of 14 of 23 ears showed involvement of the IAC. There were no significant differences in age, side of otosclerosis, or preoperative hearing threshold between the two groups. The mean postoperative AC and BC thresholds and ABG of the IAC group were significantly poorer (45.7 dB, 33.8 dB, and 11.8 dB, respectively) than those of the nonIAC group (24.1 dB, 20.0 dB, and 4.1 dB, respectively). CONCLUSIONS: Cochlear otosclerosis with cavitating lesions involving the IAC showed significantly poorer postoperative audiological outcomes than those without any cavitating lesion. Cavitation extending to the IAC may act as a third window providing a route for sound energy shunting, and thus precluding successful hearing outcome in some subjects with cavitating otosclerosis after stapedotomy.