Otosclerotic Lesions Research Articles (Page 1)

Introduction: Otosclerosis is a bone disorder affecting the labyrinthine capsule that leads to conductive and occasionally sensorineural hearing loss. The etiology of otosclerosis remains unknown; factors such as infection, hormones, inflammation, genetics, and autoimmunity have been discussed. Treatment consists primarily of surgical stapes replacement and cochlear implantation. High-resolution computed tomography is routinely used to visualize bone pathology. In the present study, we used synchrotron radiation phase-contrast imaging (SR-PCI) to examine otosclerosis plaques in a temporal bone for the first time. The primary aim was to study their three-dimensional (3D) outline, vascular interrelationships, and connections to the middle ear. Methods: A donated ear from a patient with otosclerosis who had undergone partial stapedectomy with the insertion of a stapes wire prosthesis was investigated using SR-PCI and compared with a control ear. Otosclerotic lesions were 3D rendered using the composite with shading technique. Scalar opacity and color mapping were adjusted to display volume properties with the removal of bones to enhance surfaces. Vascular bone channels were segmented, and the communications between lesions and the middle ear were established. Results: Fenestral, cochlear, meatal, and vestibular lesions were outlined three-dimensionally. Vascular bone channels were found to be frequently connected to the middle ear mucosa, perilabyrinthine air spaces, and facial nerve vessels. Round window lesions partly embedded the cochlear aqueduct which was pathologically narrowed, while the inferior cochlear vein was significantly dilated in its proximal part. Conclusion: Otosclerotic/otospongiotic lesions were imaged for the first time using SR-PCI and 3D rendering. The presence of shunts and abnormal vascular connections to the labyrinth appeared to result in hyper-vascularization, overloading the venous system, and leading to sensorineural hearing loss. We speculate about possible local treatments to alleviate the impact of such critical lesions on the labyrinthine microcirculation.

The involvement of the inner ear in otosclerosis may lead to the development of cochlear otosclerosis. The aim of this study was to analyse changes in the chemical composition and microstructure of the stapes in the course of otosclerosis compared to healthy stapes. This analysis included 31 patients with otosclerosis and 9 patients without otosclerosis. Microanalytical and diffraction techniques were used to assess the elemental distribution and orientation topography of the stapes. The concentration of Ca2+ in the study group was significantly lower in the area of the anterior crus of the stapes than in the posterior crus. A reduction in the Ca2+/P3+ ratio in the anterior crus was associated with deteriorated bone conduction and tinnitus. Degradation of the stapes microstructure in the area of otosclerotic lesions was observed with scanning electron microscopy. Bone remodelling is most significant at the closest location to typical otosclerotic lesions with hydroxyapatite porosity and scale-like bone formation according to scanning electron microscopy. There is a relationship between the disturbance of calcium metabolism and the development of clinical symptoms of cochlear 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.

ObjectivesThe objective of this study was to predict occurrence of facial nerve stimulation (FNS) in cochlear implanted patients for far‐advanced otosclerosis (FAO) by correlating preoperative computed tomography (CT)‐scan data to FNS and to evaluate FNS impact on hearing outcomes.MethodsRetrospective analysis on 91 ears (76 patients) implanted for FAO. Electrodes were straight (50%) or perimodiolar (50%). Demographic data, extension of otosclerosis on preoperative CT scan, occurrence of FNS, and speech performance were analyzed.ResultsPrevalence of FNS was 21% (19 ears). FNS appeared during the first month (21%), 1–6 months (26%), 6–12 months (21%), and over 1 year (32%) postimplantation. Cumulative incidence of FNS at 15 years was 33% (95% CI = [14–47%]). Extension of otosclerotic lesions on preimplantation CT‐scan was more severe in FNS ears compared to No‐FNS (p < .05): for Stage III, 13/19 (68%) and 18/72 (25%) ears for FNS and No‐FNS groups, respectively (p < .05). Location of otosclerotic lesions relative to the facial nerve canal was similar whatever the presence or not of FNS. Electrode array had no impact on FNS occurrence. At 1 year post‐implantation, duration of profound hearing loss (≥5 years) and previous stapedotomy were negatively associated with speech performance. FNS did not impact hearing outcomes, despite a lower percentage of activated electrodes (p < .01) in the FNS group. Nevertheless, FNS were associated with a decrease of speech performance both in quiet (p < .001) and in noise (p < .05).ConclusionCochlear implanted patients for FAO are at greater risk of developing FNS affecting speech performance over time, probably due to a higher percentage of deactivated electrodes. High resolution CT‐scan is an essential tool allowing FNS prediction but not time of onset.Level of evidence2b, Laryngoscope Investigative Otolaryngology, 2022.

Since the fissula ante fenestram (FAF) is considered as a focus of otosclerotic lesion and a route of perilymph leakage, there are few description of prenatal development of the cartilaginous canal passing though the cochlear wall. We examined the sagittal and frontal histological sections of the ear from 32 human fetuses at 8-37 weeks of gestational age. At 8-12 weeks, in the immediately anterior side of a connection between the cochlear and canalicular parts of the otic capsule cartilage, the FAF appeared as a tear of a cartilage between the basal and second turns of the cochlea. The tear became a slit opening to the scala vestibuli. At 13-15 weeks, the FAF, less than 1.2 mm in length, had the anterosuperior and postero-inferior apertures: the former was near the geniculate ganglion and became closed after 15 weeks, while the latter approached the oval window. Third trimester fetuses, the FAF, 1.5-2.0 mm in length, consistently carried a single, postero-inferior aperture extending along the anterior margin of the oval window and it contained no definite epithelium and vessel. Although it was endochondral ossification, there was no clear zonation in cartilage cells of the FAF. A mechanical stress during three-dimensional coiling of the cochlear ducts seemed to provide the FAF. After the FAF was established, the stapes footplate might use a part of the inferior aperture for the syndesmosis. A specific ossification was seen in the FAF, but it might rarely cause the pathological syndesmosis.

MRI evaluation of the endolymphatic space in otosclerosis and correlation with clinical findings

Background and Objectives: We aimed to identify prognostic computed tomography (CT) findings in retrofenestral otosclerosis, with particular attention paid to the role of otosclerotic lesion area in predicting post-stapedotomy outcome. Materials and Methods: We included 17 subjects (23 ears) with retrofenestral otosclerosis who underwent stapedotomy. On preoperative CT, the presence of cavitating lesion and involvement of various subsites (cochlea, round window [RW], vestibule, and semicircular canal) were assessed. Pre- and post-stapedotomy audiometric results were compared according to the CT findings. The surgical outcomes were analyzed using logistic regression with Firth correction. Results: Cavitating lesions were present in 15 of 23 ears (65.2%). Involvement of the RW was the strongest predictor of unsuccessful surgical outcome, followed by involvement of the internal auditory canal (IAC) and the cochlea. Conclusions: RW and IAC involvement in retrofenestral otosclerosis were shown to predict unsuccessful outcomes. While a “third window” effect caused by extension of a cavitating lesion into the IAC may dissipate sound energy and thus serve as a barrier to desirable postoperative audiological outcome, a “single window” effect due to an extension of retrofenestral otosclerosis into the RW may preclude a good surgical outcome, even after successful stapedotomy, due to less compressible cochlear fluid and thus decreased linear movement of the piston.

Otolaryngologists regularly receive invitations from open access otolaryngology–head and neck surgery journals to submit papers or to join the editorial board. Some of these journals are considered “predatory.” There has been no published attempt to see if bogus otolaryngological articles would be accepted by such journals. We sent a fake article describing a supposed otosclerotic lesion localized in the fallopian tube and surgically treated by phacoemulsification of the stapes to 41 such journals. Eight journals accepted the paper, 7 requested structural revision, 2 requested revision even though the reviewer recommended rejection, 4 rejected the paper only because they found it had already been published by another open access journal (without the authors’ knowledge), and 2 rejected the paper. Eighteen journals had not responded after 6 weeks. A contemporary retelling of the poem “The Fox and the Crow” concludes our article, which illustrates predatory practices among specific open access otolaryngology journals.

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. Retrospective study. University hospital. Forty-six ears from 37 patients with otosclerosis were included in the present study. 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. Imaging, hearing levels, and blood flow values. 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. EH was frequently present in ears with otosclerosis, especially those with severe hearing loss or advanced disease on CT.

To clarify the anatomical distribution of otosclerotic loci in otosclerosis. 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. 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. 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.

Assessing the maximum safe dose for local bisphosphonate delivery to the cochlea enables efficient delivery without ototoxicity. Otosclerosis is a disease of abnormal bone metabolism affecting the otic capsule, which can cause conductive hearing loss. Larger otosclerotic lesions involving the cochlear endosteum and spiral ligament can result in sensorineural hearing loss. Bisphosphonates are used to treat patients with metabolic bone diseases, including otosclerosis. Local delivery is the most efficient way of delivery to the cochlea while avoiding systemic side effects. To attain intracochlear bisphosphonate delivery without ototoxicity, the maximum safe dose of bisphosphonates requires definition. In the present study, we tested increasing concentrations of zoledronate, a third-generation bisphosphonate in an intracochlear delivery system. We measured ototoxicity by monitoring distortion product otoacoustic emissions and compound action potentials. Artificial perilymph and increasing molar concentrations of zoledronate were administered to the cochlea in guinea pigs via a cochleostomy. Hearing was measured at multiple time points. A fluorescently labeled zoledronate derivative (6-FAM-ZOL) was coadministered as an internal control for drug delivery. Specimens embedded in the resin blocks were ground to a mid-modiolar section and fluorescent photomicrographs were taken. No significant shift in hearing was observed in animals treated either with artificial perilymph or with 4% of the human systemic zoledronate dose. However, compound action potentials thresholds increased during infusion of 8% of the human systemic zoledronate dose, improved 4 hours later, and then increased again 4 weeks later. Using fluorescent photomicrography, intracochlear bisphosphonate delivery up to the apical cochlear turn was confirmed by visualizing 6-FAM-ZOL. These findings provide reference values for intracochlear bisphosphonate delivery in the treatment of cochlear otosclerosis and describe a useful method for tracking cochlear drug delivery.

Investigation of differential protein expression will provide clues to pathophysiology in otosclerosis. Otosclerosis is a bone remodeling disorder limited to the endochondral layer of the otic capsule within the temporal bone. Some authors have suggested an inflammatory etiology for otosclerosis resulting from persistent measles virus infection involving the otic capsule. Despite numerous genetic studies, implication of candidate genes in the otosclerotic process remains elusive. We employed liquid chromatography-mass spectrometry (LC-MS) analysis on formalin-fixed celloidin-embedded temporal bone tissues for postmortem investigation of otosclerosis. Proteomic analysis was performed using human temporal bones from a patient with severe otosclerosis and a control temporal bone. Sections were dissected under microscopy to remove otosclerotic lesions and normal otic capsule for proteomic analysis. Tandem 2D chromatography mass spectrometry was employed. Data analysis and peptide matching to FASTA human databases was done using SEQUEST and proteome discoverer software. TGFβ1 was identified in otosclerosis but not in the normal control temporal bone specimen. Aside from TGFβ1, many proteins and predicted cDNA-encoded proteins were observed, with implications in cell death and/or proliferation pathways, suggesting a possible role in otosclerotic bone remodeling. Immunostaining using TGFβ1 monoclonal revealed marked staining of the spongiotic otosclerotic lesions. Mechanisms involved in cochlear extension of otosclerosis are still unclear, but the implication of TGFβ1 is supported by the present proteomic data and immunostaining results. The established role of TGFβ1 in the chondrogenesis process supports the theory of a reaction targeting the globulae interossei within the otic capsule.

Osteogenesis Imperfecta (OI) is a genetic disorder of connective tissue matrix. OI is caused by mutations that affect type I collagen. The hearing loss in OI is characterized by onset in early adulthood and can be conductive, sensorineural, or mixed. To describe the temporal bone histopathology in 9 individuals with OI. Four adult, 1 pediatric, and 4 infant specimens were identified. Temporal bones were removed at autopsy and studied using light microscopy. All adults and 1 pediatric specimen showed otosclerotic lesions. The findings included examples of clinical, histologic, and cochlear otosclerosis. The temporal bones of infants showed delayed ossification of the endochondral layer of bone and of the ossicles. There were no infant specimens with otosclerotic lesions. Hearing loss in OI may be the result of clinical or cochlear otosclerosis. Fracture or atrophy of the ossicles may also be present in OI. A third unidentified mechanism of hearing loss may lead to cochlear degeneration. The described findings of otosclerotic lesions have implications for the observed heterogeneity of hearing loss patterns and for the surgical management of hearing loss in OI.

Detection of small fenestral otosclerotic lesions by high-resolution computed tomography using multiplanar reconstruction

To assess the use of cone beam computed tomography (CBCT) compared with multi-slice computed tomography (MSCT) in otosclerosis, with special emphasis on middle- and inner-ear anatomy. Prospective study. Twenty patients who underwent a stapedectomy 30 years ago were selected on the basis of bone conduction threshold values. Their mean age was 65 years (range, 48-76 yr). All patients underwent CBCT and MSCT with a slice thickness of 0.5 to 0.6 mm. Sixteen middle- and inner-ear anatomic structures and stapedial prostheses were analyzed by visual grading analysis. To assess critical reproduction and thereby the clinical applicability of CBCT, a dichotomization was made. Assessment of otosclerotic foci was performed using a grading system dividing the lesions in; (1) sole fenestral lesions, (2) retrofenestral lesions with or without fenestral lesions and (3) severe retrofenestral lesions. The 16 anatomic structures were clearly reproduced by both imaging techniques. However, there was an interobserver variation in judging the superiority of 1 method in favor of the other. Otosclerotic lesions were diagnosed in 80/95% using MSCT and 50/85% using CBCT (evaluators 1 and 2, respectively). Retrofenestral lesions were diagnosed in 5 of 10 of ears with severe-to-profound hearing loss, whereas no retrofenestral lesions were diagnosed in the 10 ears with mild-to-moderate hearing loss. The stapedial prostheses were adequately or very well reproduced by both methods. CBCT is a new imaging technique with a considerably lower radiation dose than conventional MSCT. Our study indicates that CBCT is suitable and, in many ways, equivalent to MSCT, for temporal bone imaging in otosclerosis.

Otosclerosis, which is characterized by disordered bone remodeling, occurs exclusively in the human temporal bone. The etiology of the disease is unknown, but a popular hypothesis is that it is caused by persistent measles virus (MV) infection. Paramyxovirus-like filamentous structures were found in otosclerotic lesions of stapes footplates from patients with otosclerosis. Although MV RNAs have been detected in otosclerotic samples by using reverse transcription-PCR, no complete MV mRNA sequence has been reported, nor has infectious virus been isolated from clinical samples. Furthermore, one study failed to obtain evidence of MV infection in otosclerotic bone samples. In this study, we tested, by three different protocols, for the presence of MV in clinical samples from patients with otosclerosis in Japan. We used a highly sensitive reverse transcription-quantitative PCR method which is able to detect viral mRNA in cells infected with MV at around one infectious unit per well. We obtained no evidence of MV infection in bone samples, primary cell cultures derived from stapes bones, or MV-susceptible cell lines (Vero/hSLAM and II-18 cells) cocultured with bone samples or primary cell cultures derived from them. Thus, our results do not support the hypothesis that persistent MV infection is involved in the pathoetiology of otosclerosis.

The objective of this study was to evaluate the histopathological incidence of facial canal dehiscence in otosclerosis cases compared with non-otosclerotic controls. 133 temporal bones from 84 otosclerosis (35 unilateral otosclerosis, 49 bilateral otosclerosis) cases were compared to 102 age-matched normal temporal bones from 70 subjects (38 unilateral normal cases, 32 bilateral normal cases). Temporal bones were serially sectioned in the horizontal plane at a thickness of 20μm, and were stained with hematoxylin and eosin. We evaluated the location and the invasion of otosclerosis to the facial canal and incidence of facial canal dehiscence under light microscopy. Facial canal was subdivided into four portions: (1) the geniculate ganglion, (2) the tensor tympani muscle, (3) the oval window, and (4) mastoid. The incidence of facial canal dehiscence in otosclerosis [66 temporal bones (49.6%)] was significantly lower than normal controls [67 control temporal bones (65.7%)] in the oval window area (P=0.019). Temporal bones with otosclerotic invasion to the thin bone of the canal were significantly less likely to have dehiscence [10 temporal bones (31.3%)] compared to the otosclerotic bones without invasion [56 temporal bones (55.5%)] (P=0.025). There was no significant difference in the incidence of facial canal dehiscence between temporal bones with and without otosclerosis in the entire segment of facial nerve. Our findings in this study suggest that otosclerotic lesions have the potential to close dehiscence of the facial canal in the oval window area.

Conclusion: This study documents that otosclerotic bone remodeling is distributed centripetally around the inner ear space whereas normal bone remodeling is distributed centrifugally. We suggest that this inverse relation reflects the unique osteo-dynamic setting of the otic capsule: since perilabyrinthine bone remodeling is extremely low, osteocyte deficiency and microcracks accumulate in excess toward the inner ear space with age. This may disrupt the osseus functional network, impede propagation of anti-resorptive signals, and precipitate otosclerotic bone remodeling with a spatial preference for older bone. Objective: To quantify the spatial distribution of otosclerotic bone around the inner ear space in order to explore a possible spatial relation with normal capsular bone remodeling. Methods: Otosclerotic lesions in 53 undecalcified human temporal bones were identified and volume data were measured with the CAST-grid system and processed by dedicated software for advanced design-based stereology. Results: The maximum volume fraction of otosclerotic bone was observed in the innermost perilabyrinthine zones of the otic capsule. The volume fraction of otosclerotic bone declined gradually but significantly from the inner ear space towards the capsular periphery with a general perilabyrinthine centripetal distribution.

To describe and discuss the midterm complications and pitfalls reported in patients with otosclerosis who received a cochlear implant. Prospective cohort study. Tertiary referral center. Fifteen patients who received a cochlear implant for otosclerosis, followed up for a minimum of 6 years. Onset of hearing loss occurred at a mean age (+/-standard deviation [SD]) of 32.6 +/- 8.6 years. Mean duration (+/-SD) of hearing loss was 26.8 +/- 7.9 years, and mean age (+/-SD) at implant surgery was 58.7 +/- 9.5 years. Before cochlear implantation, hearing thresholds were tested, and temporal bone anatomy and otosclerotic lesions were documented by high-resolution computed tomography and magnetic resonance imaging. All patients were implanted with a Med-El Combi 40 + device and a Standard Electrode Array. The number of inserted electrodes was checked by x-ray. After cochlear implantation, hearing skills were tested, fitting parameters were recorded, and complications were noted. As the disease progressed, the number of electrodes decreased, and the electrical thresholds, maximum comfort levels, and electric charge increased; these changes were more evident in the middle electrodes. Although facial nerve stimulation rate was lower than previously reported (13.3%), it increased during follow-up. Two patients (13.3%) had untreatable tinnitus. Nevertheless, all speech discrimination parameters improved significantly in all patients. Despite the need for special fitting strategies and the appearance of complications, facial nerve stimulation, and tinnitus, improvements in speech discrimination tests support the use of cochlear implantation for patients with otosclerosis.

Conclusions: The location and three-dimensional (3D) shapes of the otosclerotic foci suggest a general centripetal distribution of otosclerotic bone remodeling around the inner ear space, whereas the normal bone remodeling is distributed centrifugally. The existence of an inverse spatial relation between normal and otosclerotic bone remodeling suggests that inner ear mechanisms in control of bone remodeling may have a pathogenetic role in otosclerosis. Objectives: To explore the 3D shape of otosclerotic lesions around the inner ear space by introducing the use of 3D reconstructions and to discuss the results in a new context of temporal bone dynamics and perilabyrinthine signaling pathways. Methods: Thirty-four otosclerotic lesions from 20 decalcified human temporal bones were rendered and visualized with the public 3D ‘Reconstruct’ software. Results: The majority of otosclerotic lesions were found close to the labyrinthine space at the well-established topographical sites of predilection with a smooth demarcation against the surrounding bone. However, in addition the virtual 3D technique revealed a new perilabyrinthine anisotropy of individual otosclerotic lesions, displaying a bulky end facing the inner ear space and a volumetric decline towards the capsular periphery.