Otosclerosis

By Marcello Cherchi, MD PhD

For patients

Otosclerosis is a bone disease of the middle ear and inner ear. People with otosclerosis have problems with hearing and sometimes with balance. If your doctor suspects otosclerosis, they may check tests of hearing and balance, and may consider getting a special CT of the ear. In patients with otosclerosis who have hearing loss, some find a hearing aid to be helpful. If a hearing aid is not helpful, then an otolaryngologist may offer surgery for otosclerosis.

For clinicians

Overview

Otosclerosis is a disease of bone metabolism that can affect the middle ear and inner ear, and cause auditory and vestibular symptoms. The underlying cause of otosclerosis remains unknown. Diagnosis is based primarily on the clinical history and audiologic findings, sometimes supplemented by imaging (mostly to exclude alternative diagnoses). Vestibular impairment is variable. Most, though not all, investigators find high resolution temporal bone CT to be helpful in the diagnosis. There is less research regarding the diagnostic utility of MRI. Hearing loss can sometimes be addressed by amplification, though if this fails, then surgery (such as a stapedectomy) may be considered.

Introduction

Otosclerosis is a primary osteodystrophy (Gredilla Molinero et al. 2016) restricted to the temporal bone that involves abnormal bone metabolism that can affect the middle ear and inner ear.  Depending on the area(s) affected, this can manifest with auditory and (less commonly) vestibular symptoms.

Epidemiology

The incidence of otosclerosis has been estimated at 3 to 4 per 1000 (Declau et al. 2001).  It is significantly more common in Caucasian populations, and more common in women.

Genetics

Between 30% – 70% of patients diagnosed with otosclerosis report a family history that is positive for the diagnosis (Crompton et al. 2019). Some investigators report that familial otosclerosis may present with more rapid onset and with a higher incidence of bilaterality than non-familial otosclerosis (Crompton et al. 2019).

Several genetic loci have been associated with otosclerosis, but specific genes have not yet been identified (Ealy and Smith 2010).  Inheritance is not always in a clearly Mendelian pattern; it is thought that penetrance is incomplete.

Pathophysiologic mechanism of disease

The disorder of bone metabolism in otosclerosis comprises abnormal remodeling of bone.  Temporal bone studies recognize several histopathologic stages of otosclerosis:

1. Early phase: Otospongiosis, in which there are histiocytes, osteoblasts and osteocytes around blood vessels.  The affected areas develop abnormal bony morphology with immature “spongy” bone.
2. Transitional phase
3. Late phase: Otosclerosis.  The affected areas evolve into dense sclerotic bone.  This process narrows the blood vessels it surrounds.

Otosclerosis affects the following anatomical areas, in descending order of frequency (Crompton et al. 2019):

• 80%: Stapes footplate
• 30%: Round window
• 21%: Pericochlear region
• 19%: Anterior portion of internal auditory canal
• Less common: malleus, incus, facial canal, semicircular canals, endolymphatic duct.

When otosclerosis involves one or more components of the ossicular chain, this can interfere with the mechanical ability to transmit the kinetic energy of vibrations to the inner ear, thus resulting in a conductive hearing loss.

When otosclerosis involves the bone around the cochlea (pericochlear), sensorineural hearing loss can result.  The mechanism is not clear, since otosclerosis should only affect the bony labyrinth, not the membranous labyrinth or its contents; for this reason, some investigators have explored whether otosclerosis can affect the membranous labyrinth indirectly, such as by altering the chemical composition of perilymph or endolymph, or in some other way provoking deposition of abnormal material within the membranous labyrinth (Hayashi et al. 2006).  Several investigators, such as Harold Schuknecht, dispute even the existence of cochlear otosclerosis (Schuknecht 1979; Schuknecht and Kirchner 1974).

The underlying cause of otosclerosis has not been conclusively identified (Rudic et al. 2015).  Speculations in the literature include an intrinsic abnormality of collagen, autoimmunity, inflammation, measles infection, hormonal influences, oxidative stress and others.

Clinical presentation

Peak age of symptom onset is in the third decade, with a range of the first through the sixth decade (Crompton et al. 2019). It is relatively uncommon in the pediatric population (Daniel et al. 2023; Lescanne et al. 2008; Salomone et al. 2008; Sobolewska and Clarós 2018). Symptoms can include hearing loss, tinnitus (Danesh, Shahnaz, Hall 2018) or disequilibrium. It is not clear whether otosclerosis is capable of causing purely vestibular deficits and no auditory deficits (Cody and Baker 1978).

Most cases of otosclerosis present with gradually progressive hearing loss that can be conductive, sensorineural or mixed. The hearing loss is bilateral in 70 – 85% of cases, and often asymmetrical (Crompton et al. 2019).

Esa-Nunez and colleagues studied 40 otosclerotic patients complaining of “dizziness” and reported that, “Dizziness, although frequent in patients with otosclerosis is rarely a cause for specific clinical assessment. There is a lag between the patient’s perception of hearing loss and the initiation of vestibular symptoms” (Eza-Nunez, Manrique-Rodriguez, Perez-Fernandez 2010).

Studies reach different conclusions regarding the frequency of vestibular symptoms among otosclerosis patients.

• Grayeli and colleagues conclude that, “The proportion of patients with otosclerosis among those with balance disorders was similar to the estimated prevalence of otosclerosis in the general population” (Grayeli, Sterkers, Toupet 2009).
• Morales-Garcia studied 202 otosclerotic patients and found that 27.7% reported vestibular symptoms (Morales-Garcia 1972).
• Freeman reviewed 438 otosclerotic patients and reported that 165 (37%) had vestibular complaints (Freeman 1980).
• Yetiser reviews literature citing that 25% – 45% of otosclerotic patients have vestibular complaints (Yetiser 2018).

Physical examination

Bedside hearing tests, such as Rinne’s test, may identify conductive hearing loss.

Ocular motor examination

Patients with otosclerosis who are otherwise healthy typically have normal ocular motor examinations.

Auditory testing

Audiometric findings in otosclerosis are variable (Hannley 1993). Audiometry usually shows bilateral hearing loss that can be conductive, sensorineural or mixed. Conductive hearing loss is more common, and is sometimes the initial type (Danesh, Shahnaz, Hall 2018).  It may also show a Carhart notch (Carhart 1971), though this finding is inconsistent (Wegner et al. 2013).

Acoustic reflexes are often abnormal in otosclerosis (Forquer and Sheehy 1981, 1987), and commonly are inverted (Ried et al. 2000; Vallejo et al. 2009).

Vestibular testing

Otosclerotic patients can exhibit a variety of abnormalities on instrumented otovestibular testing.

Vestibular testing: caloric testing

Morales-Garcia studied 202 otosclerotic patients and noted that, “As the age of patients increased there was a parallel increase of deafness and the latter was accompanied by a greater cochleo-vestibular involvement. Those ears with cochlear involvement showed a greater percentage of caloric abnormalities than the ears with a purely conductive deafness” (Morales-Garcia 1972).

Cody and Baker studied 500 unoperatic otosclerotic patients and reported that, “The incidence of vestibular symptoms in patients with otosclerosis increased as the relative and absolute amounts of sensorineural hearing loss increased and was much higher than one would expect in the normal population. In addition, with increasing sensorineural hearing loss, the severity of vestibular symptoms increased along with the incidence of depression in vestibular function determined by the bithermal caloric test in patients with vestibular symptoms” (Cody and Baker 1978).

Panda and colleagues (Panda et al. 2001) studied caloric testing in 25 otosclerotic patients before and after undergoing stapes surgery. They reported that, “Patients with otosclerosis demonstrated hypoexcitability compared to controls, which was statistically significant for right cold and hot irrigation… [T]he degree of vestibular dysfunction seems to be inversely proportional to the hearing result” (Panda et al. 2001).

Vestibular testing: vibration-induced nystagmus on video oculography

Manzari and Modugno studied the effect of bone vibration in otosclerotic patients and found that this had the effect of stimulating the otosclerotic side (i.e., slow phase drifting towards the healthy ear, fast phase beating towards the affected ear) (Manzari and Modugno 2008). This pattern is reversed from the vibration induced nystagmus that would normally be seen in static vestibular lesions.

Vestibular testing: computerized dynamic posturography

Parnes and colleagues (Parnes et al. 1978) studied caloric testing and computerized dynamic posturography in 10 otosclerotic patients “before (series 1), 48 hours after (series 2), and between two to four months after (series 3) a stapedectomy.” They reported that, “There was no significant change in the electronystagmography (ENG) test findings between series 1 and 3. Posturography, however, demonstrated an uncompensated vestibular pattern in the immediate postoperative period which, after two months, converted to a compensated vestibular pattern,” and concluded that, “Posturography serves as a useful quantitative test for the study of patients with balance disorders because the procedure supplements rather than complements the ENG. In addition, posturography detects vestibular reflex abnormalities in stapedectomized patients two months afterwards” (Parnes et al. 1978).

Vestibular testing: vestibular evoked myogenic potentials

Akazawa and colleagues studied cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potentials (oVEMPs) of 17 otosclerotic patients both before and after stapes surgery and found no statistically significant change in vestibular evoked myogenic potentials (VEMPs) responses after surgery (Akazawa et al. 2018).

Amali and colleagues studied audiometry, air-conducted and bone-conducted cervical vestibular evoked myogenic potentials in the affected and unaffected ears of 30 otosclerotic patients and identified that the ears affected by otosclerosis had statistically significantly prolonged p13 latencies and reduced interpeak amplitudes. They concluded, “This study tends to suggest that due to the direct biotoxic effect of the materials released from the otosclerosis foci on saccular receptors, there might be a possibility of vestibular dysfunction in otosclerotic patients” (Amali et al. 2014).

Catalano and colleagues undertook a prospective case-control study involving 27 otosclerotic patients before and after surgery for otosclerosis using audiometry, cervical vestibular evoked myogenic potentials and video head impulse testing. They reported a statistically significantly reduced interpeak amplitude on cervical vestibular evoked myogenic potentials, and no statistically significant difference in gains on video head impulse testing, and concluded, “These findings indicate a probable traumatic saccular impairment in patients with vestibular symptoms” (Catalano et al. 2017).

Lin and Young studied audiometry, caloric testing, cervical vestibular evoked myogenic potentials and ocular vestibular evoked myogenic potentials in 50 otosclerotic patients — 27 with “vertigo” and 23 without vertigo — and concluded, “Otosclerosis patients with vertigo have more frequent abnormalities of oVEMPs to impulsive stimulation than do those without, consistent with more frequent abnormalities of the utricle. Abnormalities of oVEMPs and cVEMPs are more frequent than for caloric testing and BC hearing thresholds. SIGNIFICANCE: The relative frequency of abnormalities may reflect the degree of pathological involvement of the utricle, saccule, semicircular canals and cochlea in otosclerosis patients with vertigo” (Lin and Young 2015).

Saka and colleagues studied bone-conducted audiometry, caloric testing and cervical vestibular evoked myogenic potentials in 25 unoperated otosclerotic patients, of whom 10 had vestibular complaints and 15 did not (Saka et al. 2012). They reported that bone-conducted cervical vestibular evoked myogenic potentials were abnormal in 9 out of 10 patients (90%) with vestibular complaints, and in only 1 out of 15 patients (7%) without vestibular complaints.

Tramontani and colleagues conducted a prospective study of audiometry, caloric testing, air-conducted (AC) and bone-conducted (BC) cervical and ocular vestibular evoked myogenic potentials (VEMPs) in 126 otosclerotic ears before and after stapes surgery and concluded that, “AC and BC VEMPs can be elicited in ears with otosclerosis. AC-VEMP is more vulnerable to conductive hearing loss. Evaluation of AC-VEMP thresholds can be added in the diagnostic work-up of otosclerosis in case of doubt, enhancing differential diagnosis in patients with air-bone gaps,” and also somewhat surprisingly that, “Otosclerosis is not a cause of canal paresis or vertigo” (Tramontani et al. 2014).

Trivelli and colleagues conducted a randomized prospective trial of air-conducted vestibular evoked myogenic potentials in 41 otosclerotic patients before and after stapedotomy and concluded that “VEMPs reduced elicitability, in otosclerosis, is likely due to conductive hearing loss and inner ear impairment” (Trivelli et al. 2010).

Yang and Young studied audiometry, air-conducted and bone-conducted cervical vestibular evoked myogenic potentials in 21 ears of 15 otosclerotic patients and 20 ears of 10 healthy controls, and concluded that, “a significant relationship existed among the presence of AC-VEMPs, BC-VEMPs, and magnitude of conductive hearing loss. CONCLUSION: The presence of an AC-VEMP may indicate an earlier stage of otosclerosis, although absent BC-VEMP infers a later stage. Restated, AC-VEMPs may complement the results obtained with BC-VEMPs to classify the stage of otosclerosis” (Yang and Young 2007).

Instrumented vestibular testing in otosclerosis patients: summary

Results of studies are sometimes discrepant, but generally, otosclerotic patients are more likely than controls to exhibit abnormalities on instrumented vestibular testing such as vestibular evoked myogenic potentials, caloric testing, video head impulse testing and computerized dynamic posturography. Thus we would agree with the overall observations of Rajati and colleagues who studied results of an audiovestibular test battery (audiometry, cervical vestibular evoked myogenic potentials, ocular vestibular evoked myogenic potentials, video head impulse testing, caloric testing) in otosclerotic patients and reported that, “the vestibular system even in asymptomatic cases, is affected by otosclerosis. Furthermore, it seems that the otolithic system has a higher chance of involvement, compared to the semicircular canals” (Rajati et al. 2022).

Imaging

Most investigators find CT (usually high resolution temporal bone CT) to be helpful in diagnosing otosclerosis (Blakley et al. 1986; Brown, Mocan, Redleaf 2019; Damsma et al. 1984; De Groot et al. 1986; Fraysse 2010; Gredilla Molinero et al. 2016; Kanzara and Virk 2017; Kawase et al. 2006; Kiyomizu et al. 2004; Lagleyre et al. 2009; Lee et al. 2009; Mafee et al. 1985a; Mafee et al. 1985b; Marx et al. 2011; Miura et al. 1996; Purohit, Hermans, Op de Beeck 2014; Redfors et al. 2012; Swartz et al. 1985; Valvassori 1987; Valvassori and Dobben 1985; Vartiainen and Saari 1993; Vicente Ade et al. 2006; Wilbrand 1988; Wycherly et al. 2010; Yamashita et al. 2017; Zhu et al. 2010). A minority of investigators report that CT findings are not helpful in establishing a diagnosis of otosclerosis (Wegner et al. 2016).

Most investigators report good correlation between CT findings and audiometric findings in otosclerotic patients (Kawase et al. 2006; Kiyomizu et al. 2004; Marx et al. 2011; Swartz et al. 1985; Wilbrand 1988). A minority of investigators report that CT findings bear little or no correlation with audiometry and have no prognostic value (Vartiainen and Saari 1993).

The application of MRI in cases of otosclerosis has been less studied than CT. MRI findings in otosclerotic patients are often subtle (Goh, Chan, Tan 2002; Purohit, Op de Beeck, Hermans 2020), but some investigators still report it to be helpful in diagnosing otosclerosis (de Oliveira Vicente et al. 2015; Ziyeh et al. 1997). In contrast, other investigators find that MRI is not helpful in diagnosing otosclerosis (Laine et al. 2020). It may be that high resolution (3 Tesla) MRI without and with gadolinium contrast is more sensitive for detecting otosclerosis (Lombardo et al. 2016).

Histopathology

Temporal bone studies report a variety of histopathologic findings of vestibular relevance in otosclerosis.

• Hayashi and colleagues describe “cupular deposits” (Hayashi et al. 2006).
• Gussen described various degenerative changes (Gussen 1973) in vestibular structures.
• Sando and colleagues studied four temporal bones of two patients and reported neural degenerative changes distal to, and retrograde from, otosclerotic plaques apposed to the vestibular nerve (Sando et al. 1974).
• Richter and Schuknecht report, “It seems probable that a loss in vestibular neuronal population caused by involvement of dendritic fibers in the cribrose areas is at least partially responsible for the dysequilibrium or vestibular test abnormalities occurring in some patients with otosclerosis” (Richter and Schuknecht 1982).

Differential diagnosis

The differential diagnosis of otosclerosis includes other middle ear disorders that can cause conductive hearing loss.  If the hearing loss is predominantly sensorineural, then the differential diagnosis includes presbycusis.

Treatment

Treatment options for otosclerosis

Treatment of otosclerosis consists of:

• Observation.
• Amplification.
• Surgery (usually stapedotomy).  If a patient with otosclerosis has conductive hearing loss that interferes with their function, and if the conductive hearing loss is believed to be due to immobilization of the ossicular chain, then an otolaryngologist may consider surgery.
• There has been some literature regarding medical treatment for otosclerosis, though results of such studies are often disappointing. Examples of medical approaches include:
  • Fluoride.
  • Bisphosphonates
  • Bioflavonoids and other anti-oxidants

If a patient diagnosed with otosclerosis complains of hearing loss, then referral to audiology (to be evaluated for amplification) is appropriate. If that is unsuccessful, then referral to otolaryngology is appropriate.

If an otosclerosis patient complains of vestibular symptoms, the course of action is less clear. Some otolaryngologists maintain that surgery can be beneficial even for vestibular symptoms, but not all investigators agree on this point.

Outcomes of surgery for otosclerosis

Investigators disagree on the vestibular outcomes of otosclerotic patients who have undergone surgery. Most, though not all, investigators espouse the position that surgery for otosclerosis causes little, if any, measurable vestibular deficits.

Singbarti and colleagues studied bone-conducted cervical vestibular evoked myogenic potentials in 23 patients (25 ears) with unilateral or bilateral otosclerosis before and after stapedotomy surgery and reported that, “Stapedotomy surgery does not influence VEMPs, implying that the saccular receptors are not injured by surgery” (Singbartl et al. 2006).

Winters and colleagues studied bone-conducted ocular vestibular evoked myogenic potentials before and after stapes surgery in 27 otosclerotic patients (compared to 26 healthy controls) and concluded that, “No or undetectably little damage to the utricle is caused by both otosclerotic disease and stapes surgery” (Winters et al. 2013).

Satar and colleagues conducted a retrospective study of video head impulse testing (vHIT) in 11 otosclerotic patients who had undergone stapedotomy and 30 healthy controls. Out of the 22 ears of the 11 otosclerotic patients, 12 ears had undergone stapedotomy and 10 had not. They concludd that, “Otosclerosis and otosclerosis surgery may have some effects on SCC [semicircular canal] functions and thereby vHIT. Lateral SCC is the most affected SCC in terms of gain” (Satar et al. 2021).

Kujala and colleagues studied video oculography in 21 otosclerotic patients following oval window surgery and reported that, “The occurrence of nystagmus did not correlate with vestibular symptoms” (Kujala, Aalto, Hirvonen 2010).

Hirvonen and Aalto prospectively studied video oculography in 20 otosclerotic patients who underwent stapes surgery and reported that, “Vertigo was experienced immediately after the operation in five, floating sensation in two, and unspecific dizziness in two patients. Vestibular symptoms were mild or moderate in most patients. The occurrence of nystagmus did not correlate with vestibular symptoms (p > 0.05)” (Hirvonen and Aalto 2013).

Kujala and colleagues prospectively studied 33 otosclerotic patients before and after stapes surgery and concluded that, “Nystagmus with a low slow-phase velocity can occur in patients with otosclerosis. However, according to the video-oculographic findings and subjective symptoms, significant vestibular dysfunction seems to be rare and temporary after stapes surgery” (Kujala, Aalto, Hirvonen 2005).

Birch and Elbrond studied 925 ears of 722 otosclerotic patients who had undergone stapedectomy and reported that, “at follow-up an average of 15 years after the operation, hearing was somewhat poorer in those having spontaneous nystagmus towards the operated ear. At follow-up 17% had an abnormal caloric test” (Birch and Elbrond 1985).

De Vilhena and colleagues conducted a prospective observational study of 140 vertiginous patients who underwent stapes surgery and reported that, “vestibular disorders may remain after the immediate postoperative period” (de Vilhena et al. 2016).

Dybwik studied 108 stapedectomized ears of 96 otosclerosis patients and reported caloric weakness in 6 patients (6%) (Dybwik 1966).

Job and colleagues studied 170 otosclerotic patients who underwent surgery and reported that, “A significant negative influence on bone conduction thresholds, particularly at 2000 Hz, was associated with vestibular symptoms persisting for 7 days after the surgery. Symptoms of impaired bony labyrinth function after stapedotomy, persisting for more than 1 year, were associated with insufficient reduction of the air-bone gap and worse improvement in bone conduction thresholds at 1000 and 2000 Hz. The cause of both problems was related to a prosthesis that was too long or placed too deep in the inner ear during stapedotomy” (Job, Wiatr, Wiatr 2021).

References

Akazawa K, Ohta S, Tsuzuki K, Sakagami M (2018) Bone-conducted Vestibular-evoked Myogenic Potentials Before and After Stapes Surgery. Otol Neurotol 39: 6-11. doi: 10.1097/MAO.0000000000001619

Amali A, Mahdi P, Karimi Yazdi A, Khorsandi Ashtiyani MT, Yazdani N, Vakili V, Pourbakht A (2014) Saccular function in otosclerosis patients: bone conducted-vestibular evoked myogenic potential analysis. Acta Med Iran 52: 111-5.

Birch L, Elbrond O (1985) Stapedectomy and vertigo. Clin Otolaryngol Allied Sci 10: 217-23. doi: 10.1111/j.1365-2273.1985.tb00244.x

Blakley BW, Hilger PA, Taylor S, Hilger J (1986) Computed tomography in the diagnosis of cochlear otosclerosis. Otolaryngol Head Neck Surg 94: 434-8. doi: 10.1177/019459988609400405

Brown LA, Mocan BO, Redleaf MI (2019) Diagnostic Protocol for Detecting Otosclerosis on High-Resolution Temporal Bone CT. Ann Otol Rhinol Laryngol 128: 1054-1060. doi: 10.1177/0003489419859036

Carhart R (1971) Effects of stapes fixation on bone-conduction response. In: Ventry IM, Chailkin JB, Dixon RF (eds) Hearing measurement: a book of readings. Appleton-Century-Crofts, New York, NY, pp 116-129

Catalano N, Cammaroto G, Galletti B, Freni F, Nicita RA, Azielli C, Galletti F (2017) The role of cVEMPs and vHIT in the evaluation of otosclerosis and its eventual vestibular impairment: preliminary findings. B-ENT 13: 31-36.

Cody DT, Baker HL, Jr. (1978) Otosclerosis: vestibular symptoms and sensorineural hearing loss. Ann Otol Rhinol Laryngol 87: 778-96. doi: 10.1177/000348947808700605

Crompton M, Cadge BA, Ziff JL, Mowat AJ, Nash R, Lavy JA, Powell HRF, Aldren CP, Saeed SR, Dawson SJ (2019) The Epidemiology of Otosclerosis in a British Cohort. Otol Neurotol 40: 22-30. doi: 10.1097/MAO.0000000000002047

Damsma H, de Groot JA, Zonneveld FW, van Waes PF, Huizing EH (1984) CT of cochlear otosclerosis (otospongiosis). Radiol Clin North Am 22: 37-43.

Danesh AA, Shahnaz N, Hall JW, 3rd (2018) The Audiology of Otosclerosis. Otolaryngol Clin North Am 51: 327-342. doi: 10.1016/j.otc.2017.11.007

Daniel A, Budiono G, Rao A, Low GK, Ellis MP, Lee J (2023) Juvenile otosclerosis and congenital stapes footplate fixation. A systematic review and meta-analysis of surgical outcomes and management. Int J Pediatr Otorhinolaryngol 166: 111418. doi: 10.1016/j.ijporl.2022.111418

De Groot JA, Huizing EH, Damsma H, Van Waes PF, Zonneveld FW (1986) Computed tomography of the petrous bone in otosclerosis and Meniere’s disease. Acta Otolaryngol Suppl 434: 1-135.

de Oliveira Vicente A, Chandrasekhar SS, Yamashita HK, Cruz OL, Barros FA, Penido NO (2015) Magnetic resonance imaging in the evaluation of clinical treatment of otospongiosis: a pilot study. Otolaryngol Head Neck Surg 152: 1119-26. doi: 10.1177/0194599815574698

de Vilhena D, Gamboa I, Duarte D, Lopes G (2016) Vestibular Disorders after Stapedial Surgery in Patients with Otosclerosis. Int J Otolaryngol 2016: 6830648. doi: 10.1155/2016/6830648

Declau F, Van Spaendonck M, Timmermans JP, Michaels L, Liang J, Qiu JP, Van de Heyning P (2001) Prevalence of otosclerosis in an unselected series of temporal bones. Otol Neurotol 22: 596-602. doi: 10.1097/00129492-200109000-00006

Dybwik H (1966) Vestibular damage in stapedectomy. Acta Otolaryngol 62: 292-6. doi: 10.3109/00016486609119574

Ealy M, Smith RJ (2010) The genetics of otosclerosis. Hear Res 266: 70-4. doi: 10.1016/j.heares.2009.07.002

Eza-Nunez P, Manrique-Rodriguez M, Perez-Fernandez N (2010) Otosclerosis among patients with dizziness. Rev Laryngol Otol Rhinol (Bord) 131: 199-206.

Forquer BD, Sheehy JL (1981) Cochlear otosclerosis: acoustic reflex findings. Am J Otol 2: 297-300.

Forquer BD, Sheehy JL (1987) Cochlear otosclerosis: a review of audiometric findings in 150 cases. Am J Otol 8: 1-4.

Fraysse B (2010) Why do we include CT scanning in the evaluation of otosclerosis patients? ORL J Otorhinolaryngol Relat Spec 72: 168; discussion 169. doi: 10.1159/000272166

Freeman J (1980) Otosclerosis and vestibular dysfunction. Laryngoscope 90: 1481-7.

Goh JP, Chan LL, Tan TY (2002) MRI of cochlear otosclerosis. Br J Radiol 75: 502-5. doi: 10.1259/bjr.75.894.750502

Grayeli AB, Sterkers O, Toupet M (2009) Audiovestibular function in patients with otosclerosis and balance disorders. Otol Neurotol 30: 1085-91. doi: 10.1097/MAO.0b013e3181b0fd5d

Gredilla Molinero J, Mancheño Losa M, Santamaría Guinea N, Arévalo Galeano N, Grande Bárez M (2016) Update on the imaging diagnosis of otosclerosis. Radiologia 58: 246-56. doi: 10.1016/j.rx.2016.04.008

Gussen R (1973) Otosclerosis and vestibular degeneration. Arch Otolaryngol 97: 484-7. doi: 10.1001/archotol.1973.00780010498013

Hannley MT (1993) Audiologic characteristics of the patient with otosclerosis. Otolaryngol Clin North Am 26: 373-87.

Hayashi H, Cureoglu S, Schachern PA, Oktay MF, Fukushima H, Sone M, Paparella MM (2006) Association between cupular deposits and otosclerosis. Arch Otolaryngol Head Neck Surg 132: 1331-4. doi: 10.1001/archotol.132.12.1331

Hirvonen TP, Aalto H (2013) Immediate postoperative nystagmus and vestibular symptoms after stapes surgery. Acta Otolaryngol 133: 842-5. doi: 10.3109/00016489.2013.782106

Job K, Wiatr A, Wiatr M (2021) Association Between Postoperative Vertigo and Hearing Outcomes After Stapes Surgery for Otosclerosis. Ear Nose Throat J: 1455613211023014. doi: 10.1177/01455613211023014

Kanzara T, Virk JS (2017) Diagnostic performance of high resolution computed tomography in otosclerosis. World J Clin Cases 5: 286-291. doi: 10.12998/wjcc.v5.i7.286

Kawase S, Naganawa S, Sone M, Ikeda M, Ishigaki T (2006) Relationship between CT densitometry with a slice thickness of 0.5 mm and audiometry in otosclerosis. Eur Radiol 16: 1367-73. doi: 10.1007/s00330-005-0128-7

Kiyomizu K, Tono T, Yang D, Haruta A, Kodama T, Komune S (2004) Correlation of CT analysis and audiometry in Japanese otosclerosis. Auris Nasus Larynx 31: 125-9. doi: 10.1016/j.anl.2004.01.006

Kujala J, Aalto H, Hirvonen T (2010) Video-oculography findings and vestibular symptoms on the day of stapes surgery. Eur Arch Otorhinolaryngol 267: 187-90. doi: 10.1007/s00405-009-1024-6

Kujala J, Aalto H, Hirvonen TP (2005) Video-oculography findings in patients with otosclerosis. Otol Neurotol 26: 1134-7. doi: 10.1097/01.mao.0000179525.40156.fa

Lagleyre S, Sorrentino T, Calmels MN, Shin YJ, Escudé B, Deguine O, Fraysse B (2009) Reliability of high-resolution CT scan in diagnosis of otosclerosis. Otol Neurotol 30: 1152-9. doi: 10.1097/MAO.0b013e3181c2a084

Laine J, Hautefort C, Attye A, Guichard JP, Herman P, Houdart E, Fraysse MJ, Fraysse B, Gillibert A, Kania R, Eliezer M (2020) MRI evaluation of the endolymphatic space in otosclerosis and correlation with clinical findings. Diagn Interv Imaging 101: 537-545. doi: 10.1016/j.diii.2020.03.009

Lee TC, Aviv RI, Chen JM, Nedzelski JM, Fox AJ, Symons SP (2009) CT grading of otosclerosis. AJNR Am J Neuroradiol 30: 1435-9. doi: 10.3174/ajnr.A1558

Lescanne E, Bakhos D, Metais JP, Robier A, Moriniere S (2008) Otosclerosis in children and adolescents: a clinical and CT-scan survey with review of the literature. Int J Pediatr Otorhinolaryngol 72: 147-52. doi: 10.1016/j.ijporl.2007.10.017

Lin KY, Young YH (2015) Role of ocular VEMP test in assessing the occurrence of vertigo in otosclerosis patients. Clin Neurophysiol 126: 187-93. doi: 10.1016/j.clinph.2014.03.032

Lombardo F, De Cori S, Aghakhanyan G, Montanaro D, De Marchi D, Frijia F, Fortunato S, Forli F, Chiappino D, Berrettini S, Canapicchi R (2016) 3D-Flair sequence at 3T in cochlear otosclerosis. Eur Radiol 26: 3744-51. doi: 10.1007/s00330-015-4170-9

Mafee MF, Henrikson GC, Deitch RL, Norouzi P, Kumar A, Kriz R, Valvassori GE (1985a) Use of CT in stapedial otosclerosis. Radiology 156: 709-14. doi: 10.1148/radiology.156.3.4023230

Mafee MF, Valvassori GE, Deitch RL, Norouzi P, Henrikson GC, Capek V, Applebaum EL (1985b) Use of CT in the evaluation of cochlear otosclerosis. Radiology 156: 703-8. doi: 10.1148/radiology.156.3.4023229

Manzari L, Modugno GC (2008) Nystagmus induced by bone (mastoid) vibration in otosclerosis: a new perspective in the study of vestibular function in otosclerosis. Med Sci Monit 14: CR505-10.

Marx M, Lagleyre S, Escudé B, Demeslay J, Elhadi T, Deguine O, Fraysse B (2011) Correlations between CT scan findings and hearing thresholds in otosclerosis. Acta Otolaryngol 131: 351-7. doi: 10.3109/00016489.2010.549841

Miura M, Naito Y, Takahashi H, Honjo I (1996) Computed tomographic image analysis of ears with otosclerosis. ORL J Otorhinolaryngol Relat Spec 58: 200-3. doi: 10.1159/000276836

Morales-Garcia C (1972) Cochleo-vestibular involvement in otosclerosis. Acta Otolaryngol 73: 484-92. doi: 10.3109/00016487209138969

Panda NK, Saha AK, Gupta AK, Mann SB (2001) Evaluation of vestibular functions in otosclerosis before and after small fenestra stapedotomy. Indian J Otolaryngol Head Neck Surg 53: 23-7. doi: 10.1007/BF02910974

Parnes S, Black FO, Wall C, 3rd, O’Leary DP, Feltyberger E (1978) Vestibular system abnormalities in otosclerotic subjects. Otolaryngology 86: ORL-98-106. doi: 10.1177/019459987808600122

Purohit B, Hermans R, Op de Beeck K (2014) Imaging in otosclerosis: A pictorial review. Insights Imaging 5: 245-52. doi: 10.1007/s13244-014-0313-9

Purohit B, Op de Beeck K, Hermans R (2020) Role of MRI as first-line modality in the detection of previously undiagnosed otosclerosis: a single tertiary institute experience. Insights Imaging 11: 71. doi: 10.1186/s13244-020-00878-3

Rajati M, Jafarzadeh S, Javadzadeh R, Disfani MF, Yousefi R (2022) Comprehensive vestibular evaluation in patients with Otosclerosis: a case control study. Indian J Otolaryngol Head Neck Surg 74: 582-587. doi: 10.1007/s12070-022-03147-5

Redfors YD, Gröndahl HG, Hellgren J, Lindfors N, Nilsson I, Möller C (2012) Otosclerosis: anatomy and pathology in the temporal bone assessed by multi-slice and cone-beam CT. Otol Neurotol 33: 922-7. doi: 10.1097/MAO.0b013e318259b38c

Richter E, Schuknecht HF (1982) Loss of vestibular neurons in clinical otosclerosis. Arch Otorhinolaryngol 234: 1-9. doi: 10.1007/BF00453531

Ried E, Ojeda JP, Agurto M, Ried E, Martinez C (2000) [Inverted acoustic reflex in patients with otosclerosis]. Acta Otorrinolaringol Esp 51: 463-7.

Rudic M, Keogh I, Wagner R, Wilkinson E, Kiros N, Ferrary E, Sterkers O, Bozorg Grayeli A, Zarkovic K, Zarkovic N (2015) The pathophysiology of otosclerosis: Review of current research. Hear Res 330: 51-6. doi: 10.1016/j.heares.2015.07.014

Saka N, Seo T, Fujimori K, Mishiro Y, Sakagami M (2012) Vestibular-evoked myogenic potential in response to bone-conducted sound in patients with otosclerosis. Acta Otolaryngol 132: 1155-9. doi: 10.3109/00016489.2012.694473

Salomone R, Riskalla PE, Vicente Ade O, Boccalini MC, Chaves AG, Lopes R, Felin Filho GB (2008) Pediatric otosclerosis: case report and literature review. Braz J Otorhinolaryngol 74: 303-6. doi: 10.1016/s1808-8694(15)31105-8

Sando I, Hemenway WG, Miller DR, Black FO (1974) Vestibular pathology in otosclerosis temporal bone nistopathological report. Laryngoscope 84: 593-605. doi: 10.1288/00005537-197404000-00012

Satar B, Karacayli C, Coban VK, Ozdemir S (2021) Do otosclerosis and stapedotomy affect semicircular canal functions? Preliminary results of video head impulse test. Acta Otolaryngol 141: 348-353. doi: 10.1080/00016489.2021.1873416

Schuknecht HF (1979) Cochlear otosclerosis. A continuing fantasy. Arch Otorhinolaryngol 222: 79-84. doi: 10.1007/BF00469744

Schuknecht HF, Kirchner JC (1974) Cochlear otosclerosis: fact or fantasy. Laryngoscope 84: 766-82. doi: 10.1288/00005537-197405000-00008

Singbartl F, Basta D, Seidl RO, Ernst A, Todt I (2006) Perioperative recordings of vestibular-evoked myogenic potentials in otosclerosis. Otol Neurotol 27: 1070-3. doi: 10.1097/01.mao.0000244356.65003.42

Sobolewska A, Clarós P (2018) Surgical treatment in children with otosclerosis and congenital stapes fixation: our experience and outcome. Otolaryngol Pol 73: 23-28. doi: 10.5604/01.3001.0012.7217

Swartz JD, Mandell DW, Berman SE, Wolfson RJ, Marlowe FI, Popky GL (1985) Cochlear otosclerosis (otospongiosis): CT analysis with audiometric correlation. Radiology 155: 147-50. doi: 10.1148/radiology.155.1.3975393

Tramontani O, Gkoritsa E, Ferekidis E, Korres SG (2014) Contribution of Vestibular-Evoked Myogenic Potential (VEMP) testing in the assessment and the differential diagnosis of otosclerosis. Med Sci Monit 20: 205-13. doi: 10.12659/MSM.889753

Trivelli M, D’Ascanio L, Pappacena M, Greco F, Salvinelli F (2010) Air- and bone-conducted vestibular evoked myogenic potentials (VEMPs) in otosclerosis: recordings before and after stapes surgery. Acta Otorhinolaryngol Ital 30: 5-10.

Vallejo LA, Herrero D, Sanchez C, Sanchez E, Gil-Carcedo E, Gil-Carcedo LM (2009) [Inverted acoustic reflex: an analysis of its morphological characteristics in different physiological and pathological situations]. Acta Otorrinolaringol Esp 60: 238-52. doi: 10.1016/j.otorri.2009.01.001

Valvassori GE (1987) CT densitometry in otosclerosis. Adv Otorhinolaryngol 37: 47-9. doi: 10.1159/000414108

Valvassori GE, Dobben GD (1985) CT densitometry of the cochlear capsule in otosclerosis. AJNR Am J Neuroradiol 6: 661-7.

Vartiainen E, Saari T (1993) Value of computed tomography (CT) in the diagnosis of cochlear otosclerosis. Clin Otolaryngol Allied Sci 18: 462-4. doi: 10.1111/j.1365-2273.1993.tb00614.x

Vicente Ade O, Yamashita HK, Albernaz PL, Penido Nde O (2006) Computed tomography in the diagnosis of otosclerosis. Otolaryngol Head Neck Surg 134: 685-92. doi: 10.1016/j.otohns.2005.11.030

Wegner I, Bittermann AJ, Hentschel MA, van der Heijden GJ, Grolman W (2013) Pure-tone audiometry in otosclerosis: insufficient evidence for the diagnostic value of the Carhart notch. Otolaryngol Head Neck Surg 149: 528-32. doi: 10.1177/0194599813495661

Wegner I, van Waes AM, Bittermann AJ, Buitinck SH, Dekker CF, Kurk SA, Rados M, Grolman W (2016) A Systematic Review of the Diagnostic Value of CT Imaging in Diagnosing Otosclerosis. Otol Neurotol 37: 9-15. doi: 10.1097/mao.0000000000000924

Wilbrand HF (1988) Radioanatomy of cochlear and stapedial otosclerosis. Scand Audiol Suppl 30: 181-3.

Winters SM, Klis SF, Kool AC, Kraaijenga SA, Tange RA, Grolman W (2013) Perioperative bone-conducted ocular vestibular-evoked myogenic potentials in otosclerosis patients. Otol Neurotol 34: 1109-14. doi: 10.1097/MAO.0b013e318283969a

Wycherly BJ, Berkowitz F, Noone AM, Kim HJ (2010) Computed tomography and otosclerosis: a practical method to correlate the sites affected to hearing loss. Ann Otol Rhinol Laryngol 119: 789-94. doi: 10.1177/000348941011901201

Yamashita K, Hiwatashi A, Togao O, Kondo M, Kikuchi K, Inoguchi T, Maehara J, Kyuragi Y, Honda H (2017) Additive value of “otosclerosis-weighted” images for the CT diagnosis of fenestral otosclerosis. Acta Radiol 58: 1215-1221. doi: 10.1177/0284185116687172

Yang TL, Young YH (2007) Vestibular-evoked myogenic potentials in patients with otosclerosis using air- and bone-conducted tone-burst stimulation. Otol Neurotol 28: 1-6. doi: 10.1097/01.mao.0000244367.62567.0d

Yetiser S (2018) Bilateral Vestibulopathy Due to Severe Cochlear Otosclerosis: A Well-Known Condition Without Any Favorable Solution. Turk Arch Otorhinolaryngol 56: 174-176. doi: 10.5152/tao.2018.3347

Zhu MM, Sha Y, Zhuang PY, Olszewski AE, Jiang JQ, Xu JH, Xu CM, Chen B (2010) Relationship between high-resolution computed tomography densitometry and audiometry in otosclerosis. Auris Nasus Larynx 37: 669-75. doi: 10.1016/j.anl.2010.03.002

Ziyeh S, Berlis A, Ross UH, Reinhardt MJ, Schumacher M (1997) MRI of active otosclerosis. Neuroradiology 39: 453-7. doi: 10.1007/s002340050445