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Otosclerosis
Introduction
Otosclerosis (oto, "of the ear," and sclerosis, "abnormal hardening") is a pathological bone remodeling process that affects the middle and inner ears. It was first reported by Antonio Maria Valsalva in 1735 and subsequently described pathologically by Adam Politzer in 1839.[1] In otosclerosis, the normal, dense endochondral bone of the otic capsule around the inner ear labyrinth is replaced by irregularly laid spongy bone, which subsequently hardens and leads to fixation of the stapes footplate.[2]
Otosclerosis causes conductive hearing loss that typically presents with a normal tympanic membrane. However, a reddish blush on the promontory of the cochlea may be seen in some cases (Schwartze sign) if the tympanic membrane is clear enough.[3] Additionally, depending upon the foci of involvement within the bony labyrinth, otosclerosis may involve the cochlea, resulting in sensorineural hearing loss. Because of the frequent lack of otoscopic findings and the potentially significant hearing loss, many otolaryngologists characterize the presentation of otosclerosis with the phrase, "The doctor sees nothing, and the patient hears nothing."
Etiology
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Etiology
The etiopathogenesis of otosclerosis remains unclear. Some of the multiple hypotheses that have been postulated include:
Genetic
Many loci on chromosomes 6p, 9p, 1q, 3q, 6q, 7q, 15q, and 16q have been associated with otosclerosis. In an open genome-wide analysis, a new locus on chromosome 7q22.1 has also been identified. Additionally, other bone metabolism abnormalities, such as osteogenesis imperfecta, and multiple genes associated with bone remodeling have been considered potential causes of otosclerosis, including type I collagen (COL1A1), TGF-beta 1 (BMP2 and BMP4), angiotensin II (AGT M235T and ACE I/D), autoimmune reactions, human leucocyte antigen, inflammatory and regulatory cytokines, parathyroid hormone and expression of parathyroid hormone–related peptide receptors, and oxidative stress.[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]
Hereditary
In more than half of patients presenting with otosclerosis, there is a family history of the condition. Additionally, patients with family histories of otosclerosis tend to demonstrate earlier symptom onset. Genetic studies show that an autosomal dominant mode of inheritance with reduced penetrance (40%) and variable expressivity is found in most cases.[19][20][21][22]
Sex
The prevalence of otosclerosis is twice as great in women compared to men, suggesting the role of sex hormones.[23] However, because of the elasticity that estrogens provide to ligaments, women seem to suffer less hearing loss than men with the same degree of otosclerosis.[24][23]
Ethnicity
Otosclerosis is more common in patients of European or Indian ancestry. The condition is seen less frequently in individuals of African descent.[25][26]
Pregnancy
Pregnancy appears to exacerbate hearing loss in osteosclerosis; however, the exact nature of the relationship between pregnancy and otosclerosis remains unclear.[27]
Viral Infections
A role for measles virus infection in the pathogenesis of otosclerosis has been postulated. Measles virus ribonucleic acid has been detected in the footplate of the stapes on electron microscopy and immunohistochemical studies in 59%-100% of patients.[16][28][29][30][31][32][33][34][35][36] Moreover, vaccination against the measles virus appears to be a protective factor against otosclerosis: in 2007, Arnold et al demonstrated a ~25% lower rate of treatment for otosclerosis in Germany for the population vaccinated against measles compared with patients who were not.[37]
Other Causes
In addition to the above factors, menopause, trauma, and major surgery have been reported as either causing or aggravating otosclerosis.[27][38]
Epidemiology
The prevalence of clinical otosclerosis is around 0.04%-1% in White individuals, although histological evidence of otosclerosis may be present in as much as 10% of this group.[19][39][40] In contrast, the prevalence of histological otosclerosis in Black individuals is 1%, and in the Asian population is around 5%.[19] Otosclerosis is an early adult-onset disease with an incidence greater in women compared with men in a ratio of 2:1.[20][19] The disease starts in the third and fourth decades of life but usually does not cause hearing loss until after the fourth decade.[41] Overall, otosclerosis accounts for 5%-9% of hearing loss and 18%-22% of conductive hearing loss.[42]
Pathophysiology
Multiple etiological factors, such as otosclerosis, likely contribute to the pathogenesis of bony dyscrasias. Bone remodeling occurs within the otic capsule with bone resorption followed by bone deposition, thus replacing normal bone with spongiotic bone.[43] Though similar remodeling occurs in other bones, it is not typically seen in the otic capsule.
Early in the disease process, osteoclasts appear in the lesion, and their activity results in connective tissue replacing normal bone. Later, dense sclerotic bone forms in the areas of bony resorption. The result is disorganized bone, increased osteocytes, and widened marrow spaces with vascular and connective tissue. These marrow spaces are later replaced by dense, disorganized, sclerotic bone.
The initial lesion often appears in the area of the fissula ante fenestram, located between the oval window and the cochleariform process of the middle ear, expanding from there via vascular channels.[44] It is unclear why this region appears to be the epicenter in most cases of otosclerosis, but it may be because embryonic cartilage remnants occasionally persist in that location.[45] In most cases, lesions are limited to the anterior oval window and affect its function by calcifying the annular ligament or involving the stapes footplate. Both processes result in conductive hearing loss due to the limitation of the stapes' ability to transmit sonic vibrations. See Images. External and Middle Ear, Inner Ear, and Stapes for anatomical illustrations.
Histopathology
Grossly, otosclerotic foci appear chalky white, greyish, or yellowish. If the osteosclerotic centers are active and progressing rapidly, they may appear red due to increased vascularity (this is the etiology of the Schwartze sign).
Microscopically, the dense enchondral layer of the otic capsule appears to contain spongy bone. In immature active lesions of otosclerosis, there are abundant marrow and vascular spaces with numerous osteoblasts and osteoclasts. Additionally, a large quantity of cement substance appears bluish-grey (blue mantles of Manasse) with hematoxylin and eosin staining.[46] Less vascularity and more bone and fibrillar substance than cementum are seen in mature foci, which stain red.
History and Physical
The most frequent chief complaint of patients with clinical otosclerosis is hearing loss, although tinnitus and vertigo may also occur. Patients with otosclerosis usually present with bilateral hearing loss (~70% of patients) that has been gradually worsening over many years. Typically, the hearing loss starts in one ear and, over time, progresses to involve the other ear.
Initial symptoms of otosclerosis include decreased sensitivity to low-frequency sounds, such as whispers. Patients may also paradoxically deny difficulty hearing conversation in loud background noise, which is termed "paracusis Willisii" or "paracusis of Willis," after the 1672 description of the phenomenon by Dr. Thomas Willis of Great Britain's Royal Society.[47] Although the paracusis of Willis is not pathognomonic for otosclerosis, it is indicative of conductive hearing loss. Tinnitus may worsen as the disease progresses. Vertigo is usually mild, but as the disease progresses, balance may deteriorate, mimicking Ménière disease.[48]
On physical examination, patients with otosclerosis may speak in low volume and monotonous voices. Otoscopy may reveal no abnormalities at all. With active otosclerosis, however, increased vascularity of the cochlear promontory may be visible through the tympanic membrane (Schwartze sign).[49] However, this finding is uncommon and only apparent in around 10% of patients.[50][51]
Evaluation
Tuning Fork Testing
A Weber test performed with a 512 Hz fork will generally lateralize toward the ear with the conductive loss or toward the ear with the greater conductive loss in cases of bilateral otosclerosis. Rinne testing will reveal bone conduction to be better than air conduction with >90% sensitivity if the conductive hearing loss exceeds 30 dB in magnitude, with 30 dB being the usual threshold for meeting indications for surgical intervention.[52]
Audiometry and Tympanometry
In most cases of otosclerosis, pure tone audiometry shows low frequency decreases in air conduction thresholds. Bone conduction, however, typically remains normal. A "Carhart notch" is often seen, which is an artifactual dip in the bone conduction line by 20-30 dB at 2,000 Hz due to the resonance frequency of the ossicular chain (see Image. Audiogram for Otosclerosis).[53] After stapedectomy, the Carhart notch usually disappears. A Carhart notch may also be present in cases of incus or malleus fixation and incudostapedial joint detachment.[54] Additionally, mixed hearing loss can be seen in patients with otosclerosis, particularly with advanced disease, as the process involves the cochlear endosteum and causes sensorineural hearing loss, particularly in the higher frequencies.[55]
Speech discrimination scores and tympanometry remain normal in early otosclerosis (type A tympanogram). However, a flattening or a stiffness curve may be observed in severe cases, indicating low compliance of the ossicular chain and tympanic membrane (type As tympanogram). Tympanometry can further differentiate otosclerosis from other pathologies with low resonance, such as ossicular chain discontinuity. Stapedial reflexes may be normal in early otosclerosis as well. However, they tend to disappear in later stages along with transient evoked otoacoustic emissions, particularly in patients who have had the condition for ten years or longer.[56][57]
High-Resolution Computed Tomography
Noncontrast, high-resolution computed tomography (CT) of the temporal bones is the gold standard for diagnosing otosclerosis (see Image. Otosclerosis).[58] In more overt cases, foci of spongiotic or sclerotic bone can be identified in the area anterior to the oval window. Additionally, the extent of thickening of the stapes footplate and round window involvement will inform the preoperative planning process. In cases of cochlear otosclerosis, a "halo sign" may be seen, in which radiolucent foci extend from the fissula ante fenestram around the cochlea itself.[59] A grading system suggested by Symons and Fanning can be used to characterize the severity of otosclerosis based on CT findings:[60]
- Grade 1: Spongiotic or sclerotic lesions are limited to the vicinity of the oval and round windows, manifesting as stapes footplate thickening and/or decalcified, narrowed, or enlarged round or oval windows.
- Grade 2: There is cochlear disease, with or without oval/round window involvement, localized to either the basal turn (Grade 2A), the middle/apical turns (Grade 2B), or both the basal turn and the middle/apical turns of the cochlea (Grade 2C).
- Grade 3: Cochlear involvement is diffuse and confluent with or without involvement of the oval and/or round windows.
Treatment / Management
Medical Management
Medical treatment is primarily aimed to halt the progress of otosclerosis or to prevent disease progression. There is no medical therapy that is curative for otosclerosis. Though sodium fluoride is prescribed to slow the progression of otosclerosis, its efficacy is still controversial.[61][62] Bisphosphonates exert antiresorptive action by inducing osteoclastic apoptosis, but should not be prescribed during pregnancy.(A1)
Third-generation bisphosphonates, such as risendronate and zolendronate, as well as older medications, like etidronate, have been used to treat otosclerosis with promising results.[43][63] The newer agents appear to be most effective due to their higher potencies and lower side effect profiles.[64] Additionally, vitamin D and bioflavonoids have been reported to improve hearing in some cases, but are not consistently effective.[64](A1)
Bilateral hearing aids are also used in many patients, either alone or in combination with other treatments.
Surgical Management
The treatment of choice is stapedotomy or stapedectomy, along with the placement of a prosthesis. In these procedures, either a hole is drilled in the center of the stapes footplate with a high-speed microdrill or a laser (stapedotomy), and a prosthesis is placed between the long process of the incus and the oval window membrane via the hole in the stapes footplate, or the stapes footplate is removed partially or in its entirety and a prosthesis placed between the incus and the oval window, typically with a vein or fascia graft used to protect the oval window membrane (stapedectomy) (see Image. Incudostapedial Joint, Intraoperative view). In both procedures, the crura of the stapes are fractured, and the incudostapedial joint is divided in order to permit the removal of the stapes superstructure.[65]
Surgical treatment for otosclerosis generally produces good outcomes, irrespective of the approach employed, provided appropriate patient selection. For patients with bilateral otosclerosis, the ear with greater hearing loss is typically addressed first; both ears are not operated under the same anesthetic in order to avoid the very unlikely scenario in which total sensorineural hearing loss occurs bilaterally as a result of surgery. A 2018 review published by Cheng et al indicated comparable results between stapedotomy and stapedectomy, with a slight advantage in terms of high-frequency hearing and complication rate for stapedotomy.[66] Revision surgery, if indicated for otosclerosis, is met with mixed success and may be necessary if the first attempt fails to improve hearing. In some cases, hearing results may be insufficient, and hearing aid use may still be required.
Complications from surgery include facial paralysis (if the tympanic segment of the facial nerve is injured where it passes superior to the oval window, particularly if it is dehiscent in the middle ear and hangs over the oval window), dysgeusia (from injury to the chorda tympani nerve during removal of the scutum bone in the surgical approach to the stapes), prosthesis displacement, reparative granuloma (an inflammatory reaction that may result in sensorineural hearing loss), and vertigo (if the prosthesis is too long and stimulates the saccule).[2][67][68][69][70] In order to ensure the correct length of prosthesis and prevent vertigo, many surgeons prefer to operate under local anesthesia with the patient awake.(B2)
Differential Diagnosis
Other otologic pathologies that present with conductive hearing loss and from which otosclerosis should be differentiated include:
Prognosis
Roughly 90% of patients with otosclerosis experience considerable improvement in their hearing acuity after surgery.[79] Occasionally, there may be a few cases in which the surgery yields no particular benefits. Worsening of the hearing loss has also been reported, albeit rarely.
Additionally, there is a chance of recurrence of the conductive hearing loss, which may be due to displacement of the prosthesis out of its original position with or without fixation of the prosthesis to the surrounding bone of the oval window or stapes footplate. If revision surgery is required, hearing outcomes are likely to be worse than those obtained with primary surgery.[80][81]
Complications
Untreated otosclerosis can gradually progress to moderate-severe (50-60 dB) conductive hearing loss, but profound hearing loss is unusual; it is indicative of cochlear involvement. On the other hand, surgical management of otosclerosis can result in a total sensorineural loss in the operated ear due to technical errors or occurrence of a reparative granuloma postoperatively, but these are very infrequent occurrences. Other complications of surgery for otosclerosis include facial nerve injury, vertigo, dysgeusia, and tinnitus. The prosthesis itself may also contribute to adverse outcomes, including necrosis and erosion of the long process of the incus due to overly tight crimping of the prosthesis onto the incus, displacement of the prosthesis, and development of the aforementioned reparative granuloma.[80]
Deterrence and Patient Education
Patients with family histories of otosclerosis should consider undergoing screening audiometry to identify conductive hearing loss early and consider initiating prophylactic medical therapy, such as oral sodium fluoride supplementation. Similarly, patients who notice the appearance or worsening of hearing loss during pregnancy should undergo audiometry and consider starting sodium fluoride to delay or prevent progression of the disease.
Enhancing Healthcare Team Outcomes
Otosclerosis is an early adult-onset disease that progresses with time, ultimately leading to moderate to severe conductive hearing loss and potentially even profound sensorineural hearing loss if left untreated for long enough. Interprofessional communication and care coordination among the otolaryngologist or otologist, primary care provider, audiologist, and nursing staff will enhance overall outcomes for patients and minimize complications, particularly from surgery. Similarly, educating healthcare providers who lack experience with otosclerosis will permit prompt diagnosis and referral for specialist management, thus leading to better outcomes for patients.
Media
(Click Image to Enlarge)
External and Middle Ear. Illustrated anatomy includes the attic, incus, malleus, tympanic cavity, tensor tympani, and auditory tube.
Henry Vandyke Carter, Public Domain, via Wikimedia Commons
(Click Image to Enlarge)
Internal Ear. Illustrated anatomy includes the labyrinth, interior of right osseous labyrinth, orifice of vestibular aqueduct, fossa cochlearis, cochlear fenestra, orifice of aquaeductus cochleae, and scala tympani.
Henry Vandyke Carter, Public Domain, via Wikimedia Commons
(Click Image to Enlarge)
Left Stapes. Image A shows the left stapes' superior view. Image B shows the medial view of the left stapes' base. Structures included in these images include the head, neck, anterior and posterior crura, and base.
Henry Vandyke Carter, Public Domain, via Wikimedia Commons
(Click Image to Enlarge)
Audiogram for Otosclerosis
Contributed by Mandy Salmon
(Click Image to Enlarge)
Incudostapedial Joint, Intraoperative View. Intraoperative view of the dehiscent tympanic segment of the facial nerve (long arrow) being gently retracted to visualize the joint between the incus (short arrow) and stapes (arrowhead).
Contributed by Ryan Winters, MD
(Click Image to Enlarge)
Otosclerosis Contributed by Steve Lange, MD
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