Tinnitus caused by essential palatal tremor.

Palatal tremor (PT) is a rare cause of objective tinnitus. Symptomatic PT is caused by injuries of the Guillain-Mollaret triangle with contraction of levator veli palatini. Essential PT causes are unknown and is produced by contraction of tensor veli palatini, with pathognomonic audible ear click. This is a case report of a 36-year-old female, who developed bilateral objective tinnitus, as well as vertigo, blepharospasm, and neck tension after a free fall trauma 30 metres in the net. She was diagnosed with essential PT and treated with botulinum neurotoxin injections in the soft palate.

Endovascular occlusion of a persistent stapedial artery prior to stapedotomy: a novel approach.

BACKGROUND: The stapedial artery is an embryonic artery that transiently supplies the cranial vasculature of the human embryo. Postnatal persistence of the stapedial artery may cause conductive hearing loss and pulsatile tinnitus due to its course through the middle ear. We describe a patient with a persistent stapedial artery (PSA) managed by endovascular coil occlusion prior to stapedotomy. METHODS: A 48-year-old woman presented with left-sided conductive hearing loss and pulsatile tinnitus. Ten years earlier the patient had undergone explorative tympanoplasty, which was aborted due to a large PSA. Digital subtraction angiography was performed to confirm the anatomy and endovascular occlusion of the proximal PSA was achieved by deployment of coils. RESULTS: The pulsatile tinnitus improved immediately after the procedure. The size of the artery subsequently decreased and surgery could be performed with only a minor intraoperative bleeding. Successful stapedotomy resulted in postoperative normalization of her hearing with some minor residual tinnitus. CONCLUSION: Endovascular coil occlusion of a PSA is feasible and safe in patients with favorable anatomy and facilitates middle ear surgery. It decreases the size of the artery and minimizes the risk of intraoperative bleeding in patients with a large PSA. The future role of this novel technique in the management of patients with PSA-related conductive hearing loss and pulsatile tinnitus remains to be determined.

Transient Facial Nerve Palsy in Aviation.

INTRODUCTION: Facial nerve palsy has been observed sporadically by aviation medicine doctors in recent years. We present two case reports of patients with the rare condition of facial nerve palsy occurring during aviation, along with a review of the literature, an overview of the phenomenon and the described symptoms of the cases. PubMed® including Medline® was searched using the terms nerve palsy and aviation with no restriction. In addition, two new cases of recurrent nerve palsy are described.CASE REPORTS: We describe two case reports: A 20-yr-old woman reported recurrent transient left-sided facial nerve palsy with increased duration and intensity on four subsequent flights, and a 35-yr-old woman who reported a left-sided transient facial nerve palsy 20 min after ascent.DISCUSSION: Included in the systematic review were 17 studies. Only case report studies were found. Including the two cases of facial nerve palsy described in this article, the reviewed studies represent 23 cases of peer-reviewed facial baro-palsy in aviation (ages 10 to 62 yr old). Having baro-palsy symptoms during flight is a rare condition, and the mechanism is not well understood. Some typical characteristics and possible mechanisms are discussed. PE tube insertion of the tympanic membrane has been found to be an effective treatment; however, further studies are needed.Bloch SL, Hertz J, Klokker M. Transient facial nerve palsy in aviation. Aerosp Med Hum Perform. 2023; 94(5):404-408.

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.

Identification of Cellular Voids in the Human Otic Capsule.

The otic capsule consists of dense highly mineralized compact bone. Inner ear osteoprotegerin (OPG) effectively inhibits perilabyrinthine remodeling and otic capsular bone turnover is very low compared to other bone. Consequently, degenerative changes like dead osteocytes and microcracks accumulate around the inner ear. Osteocytes are connected via canaliculi and need a certain connectivity to sustain life. Consequently, stochastic osteocyte apoptosis may disrupt the osteocytic network in unsustainable patterns leading to widespread cell death. When studying bulk-stained undecalcified human temporal bone, large clusters of dead osteocytes have been observed. Such "cellular voids" may disrupt the perilabyrinthine OPG mediated remodeling inhibition possibly leading to local remodeling. In the common ear disease otosclerosis pathological bone remodeling foci are found exclusively in the otic capsule. We believe the pathogenesis of otosclerosis is linked to the unique bony dynamics of perilabyrinthine bone and cellular voids may represent a starting point for otosclerotic remodeling. This study aims to identify and characterize cellular voids of the human otic capsule. This would allow future cellular void quantification and comparison of void and otosclerotic distribution to further elucidate the yet unknown pathogenesis of otosclerosis.

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.

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.

Stereologic Investigation of Mastoid Air Cell Geometry: Volume, Surface Area, and Anisotropy.

OBJECTIVE: To assess mastoid geometry using computed tomography (CT) scans and design-based stereological methods. BACKGROUND: The anatomical organization of the mastoid air cell system (MACS) remains debated. Geometrical parameters have previously been determined by automated image-analysis algorithms. Stereology is an alternative approach, which has previously been applied to estimate the volume of the MACS, but has not previously been used to estimate surface area or study anisotropy. METHODS: Twenty-three clinical CT scans of aerated temporal bones obtained from various ENT patients were studied. The structural orientation and anisotropy of the MACS was investigated by test-grid rotation and rose plots. Volume, surface area, and surface area-to-volume ratio were estimated with design-based stereology. RESULTS: Anisotropy of the mastoid air cells was demonstrated by a significant difference in surface area estimates between the axial and coronal planes (p = 0.0065). Rose plots illustrated variances in surface area estimates with different grid rotations, and a minimum value in the craniocaudal direction was shown. Sampling in the axial plane provided the least variance due to anisotropy. The mean (±SD) volume and surface area estimates were 5.71 ±â€Š2.98 cm and 117 cm ±â€Š60 cm, respectively. A large biological variation was noted. The mean (±SD) surface-to-volume ratio was 20.6 ±â€Š2.8 cm. CONCLUSIONS: The stereological technique proved to be a robust method for volume and surface area estimation in clinical CT scans. The mastoid air cells constitute an anisotropic cell-system that seems to have a predominant orientation in the craniocaudal direction.

Reposition Chair Treatment Improves Subjective Outcomes in Refractory Benign Paroxysmal Positional Vertigo.

OBJECTIVES: Despite increasing utilization of reposition devices in the management of benign paroxysmal positional vertigo (BPPV), knowledge on subjective outcomes is insufficient. The objective of the present study was to evaluate subjective vertigo complaints and vertigo-associated emotional distress during reposition chair management for refractory BPPV. MATERIALS AND METHODS: This was a prospective observational cohort study of subjective and objective data of 31 patients suffering from refractory BPPV representing failed conventional repositioning treatment. At the beginning of each visit, the patients filled out the Dizziness Handicap Inventory (DHI), the Visual Analog Scale (VAS), and the Hospital Anxiety and Depression Scale (HADS). Treatment and re-evaluation were repeated every 2 weeks until the patient was declared disease-free. RESULTS: Complete remission of BPPV required a mean of two treatments. Mean DHI score decreased from 45 points prior to first treatment to 22 points by finished treatment (p<0.001). Similarly, mean VAS score was reduced from 58 to 25 points (p<0.001), and HADS decreased from 8 to 5 points (p<0.001). Patients with cupulolithiasis reported worse vertigo complaints than those with canalolithiasis. All scores correlated positively. CONCLUSION: Patients with refractory BPPV improved significantly by reposition chair management according to all subjective outcomes. Thus, the reposition device could significantly reduce disease burden in the group of patients with BPPV who failed to respond to conventional management. The strong correlation between the scores suggests VAS as a useful tool for vertigo-related patient complaints.

[Benign paroxysmal positional vertigo treatment].

Benign paroxysmal positional vertigo (BPPV) remains the most frequent cause of vertigo. The TRV chair is a mechanical device suited for optimization of managing complex cases of BPPV. Although the use of repositioning devices in the management of BPPV is increasing, no applicable guide for the TRV management of the different BPPV subtypes exists. This article presents the techniques for addressing canalolithiasis and cupulolithiasis in the TRV chair for each affected semicircular canal. In a tertiary referral centre like our unit the TRV chair is an asset in the management of BPPV.

The Dimensions of the Orbital Cavity Based on High-Resolution Computed Tomography of Human Cadavers.

Blow-out fractures affect the volume and surface area of the orbital cavity. Estimation of these values after the trauma may help in deciding whether or not a patient is a candidate for surgery. Recent studies have provided estimates of orbital volume and area of bone defect, and correlated them with the degree of enophthalmos. However, a large degree of biological variation between individuals may preclude such absolute values from being successful indicators for surgery.Stereological methods have been used to estimate orbital cavity volume in a few studies, but to date these have not been used for surface area. To authors' knowledge, this study is the first to have measured the entire surface area of the orbital cavity.The volume and surface area of the orbital cavity were estimated in computed tomography scans of 11 human cadavers using unbiased stereological sampling techniques. The mean (± SD) total volume and total surface area of the orbital cavities was 24.27 ±â€Š3.88 cm and 32.47 ±â€Š2.96 cm, respectively. There was no significant difference in volume (P = 0.315) or surface area (P = 0.566) between the 2 orbital cavities.The stereological technique proved to be a robust and unbiased method that may be used as a gold standard for comparison with automated computer software. Future imaging studies in blow-out fracture patients may be based on individual and relative calculation involving both herniated volume and fractured surface area in relation to the total volume and surface area of the uninjured orbital cavity.

The role of connectivity and stochastic osteocyte behavior in the distribution of perilabyrinthine bone degeneration. A Monte Carlo based simulation study.

Previous studies of undecalcified temporal bones labeled with fluorescent tissue time markers and basic fuchsine have documented the unique spatial and temporal patterns underlying inner ear bone development, morphology and degeneration, and has led to the identification of inner ear OPG as the candidate inhibiter of perilabyrinthine bone resorption. Resulting age related excessive matrix microdamage, osteocyte death and degeneration of the OPG signaling pathway is expected to trigger bone remodeling in the otic capsule, but when this happens the morphology of the remodeling bone is abnormal and the distribution is not entirely smooth and predictable, but rather multifocal and chaotic with a centripetal predilection at the window regions, as in otosclerosis. Based on the observed histological patterns, the fundamental preconditions of perilabyrinthine bone cell behavior can be deduced. When this information is used to generate a virtual computer representation of the cellular signaling network, the fate of the aging network can be studied by 'virtual histology' in any number of simulated 'individuals'. We demonstrate how a combination of simple osteocyte survival functions derived from histological observations and the effect of connectivity may account for gradual centripetal degeneration as well as occasional focal degeneration of the cellular anti resorptive signaling pathway around the fluid space of the inner ear and create a permissive environment for otosclerosis.

Repositioning chairs in benign paroxysmal positional vertigo: implications and clinical outcome.

The objective was to evaluate the clinical value of repositioning chairs in management of refractory benign paroxysmal positional vertigo (BPPV) and to study how different BPPV subtypes respond to treatment. We performed a retrospective chart review of 150 consecutive cases with refractory vertigo referred to our clinic within a 10-month period. The BPPV patients were managed with classical manual manoeuvres, the Epley Omniax(®) rotator (EO) or the TRV chair (TRV). In addition, a comprehensive review of the literature was performed. BPPV was identified in 95 cases. The number of needed treatments for posterior canalolithiasis versus posterior cupulolithiasis, horizontal cupulolithiasis and multi-canal affection was significant (p < 0.01). Thirty-seven (38 %) patients required only one repositioning manoeuvre and the overall symptom relief was 91.7-100 % after 3 treatments. Eleven patients (12 %) experienced relapse within the ½-year follow-up period. Horizontal cupulolithiasis and multi-canal affection constituted the most resilient cases. The literature search identified 9 repositioning chair studies. The EO and the TRV are highly valuable assets in diagnosis and management of BPPV of particularly complex and refractory cases. However, further validation is anticipated through controlled clinical trials.

Prevalence, size and distribution of microdamage in the human otic capsule.

CONCLUSIONS: Age-dependent microdamage (MDx) accumulates excessively in human perilabyrinthine bone, where the bone turnover is almost absent. This may have pathological implications for bone-specific disorders such as otosclerosis. The role of MDx accumulation is discussed from an osteodynamic perspective. OBJECTIVES: Bone remodelling is highly inhibited within the otic capsule compared with the rest of the skeleton. Consequently excessive accumulation of age-dependent capsular MDx is expected. This study describes the prevalence, size and topographical distribution of MDx in the human otic capsule. METHODS: A total of 241 undecalcified human temporal bones were examined. Bulk staining and the cutting-grinding technique were used to separate in vivo MDx from microcrack artefacts induced post mortem by the milling procedure. Quantitative data were obtained by fluorescence microscopy by counting and measuring and by the use of stereology. RESULTS: Microcracks accumulated continuously and extensively in the human otic capsule throughout life. Both the number and total length of MDx were higher close to the inner ear space as compared with the capsular periphery. The mean length of the MDx remained constant with age. There was no statistically significant sex difference.

Labyrinthitis Ossificans: On the Mechanism of Perilabyrinthine Bone Remodeling.

INTRODUCTION: It has been suggested that remodeling of the otic capsule is highly suppressed by the action of anti-resorptive signals emanating from structures of the inner ear space. Labyrinthitis ossificans (LO) is a severe complication to bacterial meningitis and is characterized by destruction of inner ear structures by the formation of new bone. The aim of this study was to explore the impact of LO on bone remodeling of the otic capsule. MATERIAL AND METHODS: In 11 human temporal bones with extensive LO and 10 control specimens, the degree of bone remodeling was explored indirectly by estimating the viability of osteocytes in perilabyrinthine bone and the mastoid. RESULTS: The viability of osteocytes was significantly lower in the perilabyrinthine bone compared to the mastoid in both groups. However, the loss of perilabyrinthine osteocytes was the same in the 2 groups, and the presence of cartilage remnants appeared to be the same. CONCLUSION: This study indicates that the factors affecting bone remodeling of the otic capsule and the degeneration of osteocytes are not altered by wholesale destruction of inner ear soft tissue and its replacement by bone. Therefore, alternative mechanisms may be implicated in the suppression of capsular bone remodeling.

Unbiased stereologic estimation of the spatial distribution of Paget's disease in the human temporal bone.

BACKGROUND: It has been suggested that Paget's disease of bone and otosclerosis may share a myxoviral etiology. However, the association between virus infection and pathologic bone remodeling is still controversial. The aim of this study was to estimate the spatial distribution of pagetic bone remodeling around the inner ear space and to compare it with that of otosclerosis in a contemporary context of temporal bone dynamics. MATERIALS AND METHODS: From the temporal bone collection of Massachusetts Eye and Ear Infirmary, 15 of 29 temporal bones with Paget's disease were selected to obtain an independent sample. All volume distributions were obtained along the normal axis of capsular bone remodeling activity by the use of vector-based stereology. RESULTS: Pagetic bone remodeling was distributed centrifugally around the inner ear space at the individual and the general level. This pattern is similar to the normal distribution of perilabyrinthine bone remodeling but entirely different from the spatial location of otosclerosis, which are focal and centripetally distributed around the inner ear space. CONCLUSION: In Paget's disease, the antiresorptive barrier around the inner ear space becomes gradually overruled as pagetic bone resorption invades the otic capsule from the outside. However, in otosclerosis, this barrier has somehow failed locally inside the otic capsule. Although virus infections potentially may trigger osteoclastic activity additional pathogenetic factors are needed to explain the organ-specific nature and spatial properties of otosclerosis.

On the biology of the bony otic capsule and the pathogenesis of otosclerosis.

In human otosclerosis, focal pathological bone remodeling occurs in significant amounts inside the normally anti-resorptive perilabyrinthine domain of the bony otic capsule. Otosclerosis causes hearing loss in 0.2-0.5% of the population by ankylosis of the footplate. The disease cannot be predicted, avoided or medically reversed as the pathogenesis remains unknown. Previously genetic research has failed to identify a specific otosclerosis-gene and earlier theories of virus infections, autoimmunity or association to generalized bone diseases have been unable to explain why otosclerosis only occurs in the bony otic capsule while the rest of the skeleton remains completely normal. Studies from the otopathological laboratory (RH) have revealed how the bone turnover rates increase centrifugally from a sub-normal 0.1% adjacent to the inner ear space towards a normal 10% per year at the capsular periphery. This graded restriction of bone remodeling is most likely caused by the anti-resorptive action of the cytokine osteoprotegerin (OPG), which is expressed in high levels (1000 x normal bone levels) by inner ear structures to inhibit perilabyrinthine osteoclast formation and function. OPG knockout mice develop excessive, irregular bone remodeling, stapes fixation and progressive hearing loss. The lacuno-canalicular porosity is the candidate anatomical routes for the transmission of OPG-derived signals to the surrounding bone. This extracellular signaling pathway depends crucially on the viability of individual osteocytes. When bone remodeling is low, the average age of the bone matrix and osteocytes increases. We detected a high fetal density of labyrinthine osteocytes, which may secure a life-long anatomical route for inner ear OPG despite accumulation of non-viable osteocytes. Moreover, 3-D reconstructions and vector-based stereology revealed a co-existence between non-viable osteocytes and otosclerosis. We suggest that bone remodeling may commence when the effect of anti-resorptive OPG fails locally within regions of non-viable osteocytes. A sustained OPG signal from surrounding osteocyte survivors might distort the process and account for the otosclerotic morphology.

The viability of perilabyrinthine osteocytes: a quantitative study using bulk-stained undecalcified human temporal bones.

Bone remodeling is highly inhibited around the inner ear space, most likely by the anti-resorptive action of the inner ear cytokine osteoprotegerin (OPG) entering perilabyrinthine bone through the lacuno-canalicular porosity (LCP). This extracellular signaling pathway depends on the viability of individual osteocytes. The objective of this study was to evaluate the patency of the LCP at different ages. Sixty-five bulk-stained undecalcified human temporal bones and 19 ribs were selected to span the ages from the 30th gestational week to 95 years. Osteocytes from inside a 2-mm wide perilabyrinthine zone of bone were identified by 3D vector calculations and the numerical densities estimated with an optical dissector and compared to age-matched ribs. From a high fetal count of 90,000 cells/mm(3), the density of viable capsular osteocytes declined rapidly to 73,000 cells/mm(3) at three years of age, and non-viable osteocytes increased inversely. After 3 years, this decline/increase continued at a much slower rate. The densities of viable as well as non-viable osteocytes and the rates of change were much higher in perilabyrinthine bone compared to ribs. Only after the age of 80 years had the density of viable capsular osteocytes declined to the level of ribs. The bi-phasic osteocyte kinetics reflects different development stages. The high initial density of viable osteocytes may secure a life-long anatomical route for inner-ear OPG despite the unique accumulation of non-viable osteocytes. Clustering of non-viable osteocytes may cause local aberrations in the signaling system by closure of the LCP.

Otosclerosis: a perilabyrinthine threshold phenomenon.

This paper is a review of our most recent findings concerning the osteo-dynamics of the bony otic capsule and pathogenesis of otosclerosis. By exploring the spatial relationship between normal perilabyrinthine bone remodeling, the viability and spatial distribution of labyrinthine osteocytes, and the location of otosclerosis, a unique spatial pattern emerged. Bone remodeling is highly inhibited around the inner ear space. Most likely, inner ear anti-resorptive signals enter the bony otic capsule through the lacuno-canalicular porosity. The patency of this signaling pathway depends on the viability of individual osteocytes. In the young otic capsule the density of viable osteocytes is high and centripetally distributed. This arrangement may sustain a life-long osseus pathway for anti-resorptive signals even within a bone where a considerable loss of viable osteocytes must be expected, as demonstrated by a centripetal accumulation of dead osteocytes with age. The spatial distribution of dead osteocytes follows the same general pattern as otosclerosis. We suggest that clustering of dead osteocytes may impede the transmission of anti-resorptive signals locally, leaving such ghost regions susceptible to focal bone remodeling as in human otosclerosis. The preserved network of viable osteocytes around the depleted ghost regions may contain the process and distort the structure of bone remodeling into an abnormal otosclerotic pattern.