Labyrinthitis ossificans (LO) is the pathologic formation of new bone within the lumen of the otic capsule and is associated with profound deafness and loss of vestibular function. Cochlear ossification in this disease generally does not cross the endosteal layer or alter the architecture of the enchondral bone. Radiography can be used to help diagnose the condition; ceftazidime is a first-line agent for the prevention of otogenic and meningogenic labyrinthitis.
The human osseous labyrinth is composed of endosteal, enchondral, and periosteal layers. The endosteal layer consists of bone lined with a single thin layer of cells that have numerous gaps that separate them. The enchondral layer is unique in that it reaches adult size by 23 weeks' gestation and undergoes minimal remodeling after age 2 years. The periosteal layer consists of lamellar bone and is capable of remodeling and repair.
In the absence of a pathologic condition, the lumen within the otic capsule remains stable in size and patency throughout life; however, in various diseases (eg, Paget disease of bone, osteopetrosis, otosclerosis, trauma, inflammatory and infectious conditions), new disorganized bone replaces healthy bone or obliterates spaces within the otic capsule.
Labyrinthitis ossificans (LO) most commonly occurs as a sequela of inflammation of the inner ear that results from bacterial meningitis and subsequent purulent labyrinthitis. Other etiopathologic causes of labyrinthitis ossificans (LO) include vascular obstruction of the labyrinthine artery, temporal bone trauma, autoimmune inner ear disease, otosclerosis, leukemia, and tumors of the temporal bone. In addition, suppurative labyrinthitis associated with otitis media can cause labyrinthitis ossificans (LO).
Until recently, labyrinthitis ossificans (LO) was diagnosed histologically; however, radiography currently is a tool that can be used to help diagnose the condition. Radiographic documentation of osteoneogenesis within the cochlea is possible with a high-resolution computed tomography (HRCT) scan of the temporal bone.
Ceftazidime is a first-line agent for the prevention of otogenic and meningogenic labyrinthitis because it reaches higher concentrations in the perilymph and cerebrospinal fluid (CSF) than other CSF-penetrating agents (eg, cefuroxime, cefotaxime).
Steroids have been shown to inhibit the synthesis of connective tissues, impair the formation of granulation tissue, and decrease total collagen formation; however, these effects may be indirect sequelae of inflammatory suppression. Several human and animal studies have demonstrated that steroid-induced immunosuppression may reduce hearing loss associated with bacterial meningitis.
The occurrence of ossification virtually guarantees that hearing will not be restored, making cochlear implantation an important treatment option. Cochlear implants are used in patients with bilateral profound deafness. Cochlear implantation involves the insertion of an electrode array along the scala tympani beginning in the basal turn of the cochlea adjacent to the round window.
Labyrinthitis ossificans (LO) is the pathologic ossification of spaces within the lumen of the bony labyrinth and cochlea that occurs in response to a destructive or inflammatory process.[1] Regardless of the etiology, the most common region of cochlear ossification is the scala tympani of the basal turn, with the most extensive disease noted in postmeningitic cases. Fibrosis and ossification of the scala tympani are seen in the image below.
View Image | Fibrosis and ossification of the scala tympani are shown. F, fibrosis; O, osteoneogensis (hematoxylin and eosin stain). |
A retrospective study by Buch et al found that no matter the cause of labyrinthitis ossificans, including chronic otomastoiditis, temporal bone surgery, temporal bone trauma, sickle cell disease, or meningitis, the most severe effect was seen in the semicircular canals, and the least severe in the vestibule. In addition, a distinct mineralization pattern was found in patients who had undergone temporal bone surgery, with mineralization being significantly greater in the basal turn of the cochlea, the vestibule, and the semicircular canals.[2]
Studies of the pathophysiology of deafness after meningitis suggest that an inflammatory labyrinthitis develops from the spread of infection into the inner ear via the cochlear aqueduct or internal auditory canal. In 1991, Bhatt et al proposed an animal model of pneumococcal meningitis that strengthened the hypothesis that the most likely conduit of meningogenic labyrinthitis is extension of the disease through the cochlear aqueduct.[3] Because the cochlear aqueduct drains into the scala tympani adjacent to the round window, the initial concentration of inflammatory mediators occurs in this region, perhaps explaining the predominant degree of injury in this area. Another possibility for the disproportionate degree of ossification in the scala tympani of the basal turn is the relative decreased blood flow in this area. This decreased perfusion explains the propensity to develop ossification in this area, regardless of the underlying etiology.
Paparella and Sugiura outlined the pathologic stages associated with purulent labyrinthitis and the process leading to ossification of the labyrinth in laboratory animals and human beings.[4] They divided the evolution of labyrinthitis ossificans (LO) into 3 characteristic stages: acute, fibrous, and ossification. The image below depicts the stages of ossification.
View Image | Stages of ossification are shown. This histological specimen was obtained 3 months after induction of labyrinthitis. F, fibrosis; O, osteoid; C, calco.... |
The acute stage is characterized by purulence that fills the perilymphatic spaces but spares the endolymphatic space, followed by serofibrinous exudate. The second stage, or fibrous stage, consists of fibroblastic proliferation within the perilymphatic spaces, which begins approximately 2 weeks after the onset of infection. Angiogenesis is also present. The third, or ossification, stage is characterized by bone formation first observed in the basal turn of the cochlea as early as 2 months after the onset of infection. Ossification of the scala tympani is seen in the image below.
View Image | Ossification of the scala tympani is shown. |
Formation of osteoid with subsequent mineralization and remodeling obliterates the perilymphatic and endolymphatic spaces. Ossification in humans has been noted to occur within a year after meningitis, although the hearing loss may occur as early as 48 hours after infection.
In 1998, Brodie et al developed a gerbil model of labyrinthitis ossificans (LO) subsequent to Streptococcus pneumoniae–induced meningitis.[5] This model demonstrates 3 main histological features: fibrosis, osteoid deposition, and osteoneogenesis. Osteoid deposition appears as homogenous, eosinophilic, and moderately cellular deposits and occurs more prominently in areas of denser fibrosis. Osteoneogenesis that involves calcification of the bone matrix and subsequent remodeling develops adjacent to the endosteal layer within the cochlea, with preservation of the normal contour of the otic capsule.
Using the same model, Nabili and Brodie documented the occurrence of osteoneogenesis and mineralization as early as 21 days postinfection, and new bone growth was shown to be active for at least 12 months.[6] This study was extended by Tinling et al in 2004 to show osteoid deposition and mineralization occurring as early as 3 days postinfection and continuing at least through the first 28 days postinfection.[7] Resorption of new bone and remodeling by 84 days postinfection was not apparent.
In another study, Nadol et al documented that severe inflammation occurs in the scala tympani of the basal turn where the aqueduct enters the cochlea.[8] They found that reduction in the inflammatory response in the internal auditory canal occurs as it proceeds from medial to lateral. This study also documented the preservation of auditory nerve fibers despite the intense labyrinthitis and ossification with accompanying degenerative changes in the stria vascularis and organ of Corti. The number of remaining spiral ganglion cells was shown to be inversely proportional to the severity of new bone formation.
A study by Kaya et al found that compared with controls, patients in the study with labyrinthitis ossificans (LO) had a significantly lower mean density of type I and II vestibular hair cells, dark cells, and transitional cells, a change that could signal an effect on vestibular function.[9]
The phenomenon of labyrinthitis ossificans (LO) was recognized as early as the 19th century; however, the pathogenic mechanisms remain poorly understood. Early theories divided new bone formation into 2 types: metaplastic and osteoplastic. Metaplastic bone originates from scar or granulation tissue that has filled the bony labyrinth. Osteoplastic bone forms as an extension from the endosteum that lines the lumen of the otic capsule.
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Bacterial meningitis, which affects an estimated 15,000 infants and children in the United States each year, is the most common cause of both acquired sensorineural hearing loss in childhood and labyrinthitis ossificans (LO). The reported incidence of hearing loss following meningitis ranges from 6-37%, with an estimated 5% suffering from profound deafness. Deafness results from spread of the infection to the labyrinth and consequent end organ damage. Ossification within the labyrinth compounds destruction of neural elements.
Dodge et al reviewed the outcome of 185 infants and children with meningitis and found a 10% overall incidence of hearing loss.[10] The incidence of hearing loss was greatest with S pneumoniae (31%) infection and lowest with Haemophilus influenzae (6%) infection. The mortality rate of S pneumoniae –induced meningitis (19% in children, 20-30% in adults) also is the highest of the 3 infecting organisms (see the Causes section). As many as 80% of patients with profound postmeningitic deafness have some degree of labyrinthine ossification. Complete ossification is associated with a very poor prognosis for residual hearing.
See the list below:
Until recently, labyrinthitis ossificans (LO) was diagnosed histologically; however, radiography currently is a tool that can be used to help diagnose LO. Radiographic documentation of osteoneogenesis within the cochlea is possible with a high-resolution computed tomography (HRCT) scan of the temporal bone. In the image below, labyrinthitis ossificans is seen on axial CT scan.
View Image | Labyrinthitis ossificans is shown on axial CT scan. |
In the image below, labyrinthitis ossificans is depicted with right cochlea enhancement.
View Image | Labyrinthitis ossificans is depicted with right cochlea enhancement. |
In one study, some degree of abnormality of the inner ear was noted in 71% of 31 CT scans performed in cochlear implant candidates. Five scans were interpreted as showing ossification within the cochlea. Of these scans, 4 were confirmed at surgery with 1 false-positive result and 1 false-negative result among the 26 scans interpreted as not ossified (4%).
Other authors note a high incidence (63-73%) of CT scan evidence of postmeningitic patients with deafness.[13, 14, 15] They point out that ossification may not always be evident radiographically, with false-negative rates as high as 46%. The high rate of false-negative results may be related to the inability of HRCT scans to detect early histological features of fibrosis and osteoid deposition, which are consistent with the early stages of labyrinthitis ossificans (LO) prior to calcification. Despite the exquisite bone detail, HRCT scans may not detect early ossification and soft tissue abnormalities in up to 57% of patients.
Arriaga and Carrier conducted a study that suggested high-resolution, fast spin-echo, T2-weighted magnetic resonance imaging (MRI) is clinically helpful in cochlear implant candidates.[16] This type of MRI study can identify cochlear soft tissue abnormalities in areas of residual cochlear patency in cases of LO. These are soft tissue abnormalities that may not be detected on HRCT scan. This prospective study of 13 consecutive patients receiving preoperative, high-resolution, fast spin-echo, T2-weighted MRI scans of the temporal bone identified unanticipated cochlear fibrosis in 1 patient, vestibular schwannoma in 1 patient, and patency in the second turn of the cochlear in a patient with labyrinthitis ossificans (LO).
The study also disproved cochlear fibrosis suspected on HRCT imaging in 1 patient. These findings suggest that, in addition to HRCT scans, high-resolution, T2-weighted MRI studies of the temporal bone may be useful preoperatively when considering candidates for cochlear implantation.
A study by Jiang et al also suggested that MRI can aid in the assessment of cochlear implant candidates. The use of MRI in 188 patients being evaluated for implants revealed otic capsule or vestibulocochlear nerve pathologies in 17 (9%) of them, uncorrelated by audiogram findings, including, in two cases, labyrinthitis ossificans. Other findings included vestibular schwannomas (5 patients), enlarged vestibular aqueducts (4 patients), hypoplastic cochlear nerves (2 patients), cochlear aplasia (1 patient), posterior semicircular canal malformation (1 patient), calcified meningioma (1 patient), and cholesterol granuloma (1 patient).[17]
However, the value of MRI in preoperative assessment of candidates for cochlear implantation is not universally accepted.
Ceftazidime is a first-line agent for the prevention of otogenic and meningogenic labyrinthitis because it reaches higher concentrations in the perilymph and CSF than other CSF-penetrating agents (eg, cefuroxime, cefotaxime).
Steroids have been shown to inhibit the synthesis of connective tissues, impair the formation of granulation tissue, and decrease total collagen formation; however, these effects may be indirect sequelae of inflammatory suppression. Several human and animal studies have demonstrated that steroid-induced immunosuppression may reduce hearing loss associated with bacterial meningitis. Lebel et al found that treatment with dexamethasone caused a statistically significant reduction in subsequent hearing loss.[18] This finding applied only to meningitis that was caused by H influenzae. The mechanism of effect of dexamethasone on meningitis is unknown, but it is hypothesized to result from inhibition of internal mediators of inflammation (eg, interleukin [IL]–1, cachectin, prostaglandins).
Using rabbits with experimental pneumococcal meningitis, Kadurugamuwa et al showed that dexamethasone significantly lowered concentrations of prostaglandin E2 (ie, dinoprostone) in CSF and reduced mortality and clinically evident neurologic sequelae.[19] Hartnick et al performed a retrospective study of 10 patients with pneumococcal meningitis who received cochlear implantation for bacterial meningitis–related deafness.[20] Only 1 of 6 patients who received steroid therapy at the time of initial illness had evidence of LO, although all 4 patients who did not receive steroids developed LO, suggesting a role for steroids in preventing LO in children with pneumococcal meningitis.
However, the efficacy of steroid treatment in children with pneumococcal and meningococcal meningitis has not been proven; its routine administration in all cases of bacterial meningitis remains controversial. In a rabbit model, Tuomanen et al demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) reduced the incidence of hearing loss when administered early in the course of meningitis.[21]
S pneumoniae infection carries the highest incidence of associated labyrinthitis ossificans (LO). The immunogenicity of the S pneumoniae cell wall has been implicated in likelihood of developing labyrinthitis ossificans (LO). In the acute stage, components of the bacterial cell wall trigger local host defenses, which produce a vigorous inflammatory response. In addition, S pneumoniae–induced meningitis is generally treated with bacteriocidal antibiotics that induce hydrolysis of the cell wall and resultant amplification of the inflammatory response. These subcomponents of cell wall teichoic acids are potent activators of the alternative complement pathway. An excessive degree of inflammation can result from the explosive release of these cell wall subcomponents and subsequent activation of the complement cascade.
Plasma-activated complement 5 (C5a), produced from the final complement pathway, is a potent chemotactic agent for neutrophils and monocytes. Under normal conditions, CSF contains very little complement; however, the CSF contains low levels of complement if the blood-brain barrier is compromised or if astroglia produces complement as a result of infection. In 1999, DeSautel and Brodie conducted a study in which decomplementation demonstrated a reduction of the degree of labyrinthitis ossificans (LO) in experimental animals.[22] Thus, the study supported the fact that the cell wall teichoic acids from S pneumoniae initiated the vigorous immune response, which contributed to the production of cochlear fibrosis and ossification.
In addition to activation of the alternative pathway of the complement cascade, data from in vivo experiments indicated that S pneumoniae cell wall components activate monocytes, leukocytes, cerebrovascular endothelial cells, and astrocytes. These cells in turn produce various proinflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-8, platelet-activating factor, and tumor necrosis factor (TNF)–α and express specific receptors on their surface. Teichoic and lipoteichoic acids bind to acute-phase reactant C-reactive protein, activate procoagulant activity on the surface of endothelial cells, induce cytokines, and initiate the influx of leukocytes.
These cytokines and receptors initiate an accelerating cascade of events, resulting in alterations of the blood-brain barrier, polymorphonuclear leukocyte and serum protein infiltration, meningeal inflammation, increased intracranial pressure, and decreased cerebral vascular perfusion.
Yeung et al developed a technique for CSF irrigation in gerbils that have S pneumoniae meningitis to demonstrate that the dilution of inflammatory mediators in the CSF of animals with bacterial meningitis substantially diminished the amount of subsequent hearing loss and cochlear damage.[23] This method of CSF irrigation that attenuates the inflammatory mediators as a whole sets the stage for further experiments focused on the inhibition of specific mediators and their role in the pathophysiology of this type of hearing loss.
Subsequently, Ge et al investigated the role of oxygen free radicals in the pathogenesis of sensorineural hearing loss after bacterial meningitis.[24] They found that the administration of superoxide dismutase, an oxygen radical scavenger, significantly reduced hearing loss, cochlear fibrosis, spiral ganglion cells loss, and damage to cochlear components to near baseline values in a gerbil model. Aminpour et al demonstrated that blockade of TNF-α also resulted in hearing loss and cochlear injury similar to bacterial meningitis.[25] This study provides further insight into the role of cytokines in hearing loss and cochlear injury that accompany S pneumoniae meningitis and may provide a new way of preventing cochlear damage in patients with this disease.
The clinical significance of labyrinthitis ossificans (LO) increased dramatically with the advent of the cochlear implant. The occurrence of ossification virtually guarantees that hearing will not be restored, making cochlear implantation an important treatment option. Cochlear implants are used in patients with bilateral profound deafness. Cochlear implantation involves the insertion of an electrode array along the scala tympani beginning in the basal turn of the cochlea adjacent to the round window.
Dramatic benefits can be achieved in a large percentage of patients but not in all patients.[26] Factors that adversely influence the success of cochlear implantation include the number of residual spiral ganglion cells, partial vs complete electrode insertion, and duration of deafness prior to implantation. The loss of spiral ganglion cells is correlated with the degree of fibrosis and ossification. Ossification in labyrinthitis ossificans (LO) occurs primarily in the scala tympani of the basal turn of the cochlea. This location is the site of entry of the electrode array and, consequently, may interfere with full insertion and optimal performance. The electrode array is used to stimulate the residual spiral ganglion cells throughout the modiolar region.
Historically, ossification of the basal turn of the cochlea was considered a relative contraindication for cochlear implantation of a multichannel device. Options included not undergoing surgery, implantation of an extracochlear device, or placement of a single channel device. Several options and techniques for dealing with partial or total cochlear occlusion have been described. In cases of moderate ossification in which osteoneogenesis is limited to the first few millimeters of the basal turn near the round window, a complete electrode insertion can be accomplished.
Through the conventional facial recess approach, drilling takes place through the ossified portion of the basal turn until a patent lumen is reached. In severe cases, the device may be inserted partially. However, the stability of a partially inserted electrode positioned in the basal turn is less reliable and may be threatened by continual osteoneogenesis. Therefore, if implantation through the conventional approach is not favorable because of severe ossification, a circumodiolar trough for the electrodes may be created through an extended transtympanic approach at the initial surgery or as a revision.
Balkany et al have shown that drill out of the basal turn of the cochlea for partial obliteration has results that do not differ significantly from the results of patients with patent cochleas.[27] Gantz et al first reported radical cochleostomy for advanced labyrinthitis ossificans (LO) whereby the modiolar region of the cochlea is skeletonized and electrodes are draped around this area to achieve proximity to surrounding spiral ganglion cells.[28] They successfully performed implantation in 2 such patients with multichannel Nucleus devices. One of the recipients did not benefit from the device, but the other was reported to perform in a manner similar to other multichannel implantees who underwent no drill out.
Lambert et al reported the use of the Gantz radical cochleostomy technique to perform implantation in a 4-year-old child with advanced LO who was ultimately able to use 10 of 22 electrodes with apparent communication benefit.[29]
Steenerson and Gary subsequently reported that 3 patients with LO who underwent implantation using the Gantz radical cochleostomy had some benefit from the device.[30] Closed-set speech discrimination improved in one patient, but open-set audiometry was unchanged. Another patient showed some pattern recognition but had no open-set recognition, and the third patient, a small child, demonstrated behavioral evidence of auditory perception but was too young to assess discrimination.
Thus, in 5 of 6 reported cases of radical cochleostomy for labyrinthitis ossificans (LO), patients have achieved some auditory perception, but only one patient seems to have significant auditory-only speech perception.
Rauch et al reported on the results of Nucleus 22 cochlear implantation performed in 13 patients with postmeningitic deafness.[31] Thirty-one percent have severe labyrinthitis ossificans (LO) that requires radical drill out, 38% have some bone growth that requires partial drill out, and 31% have normal insertion with no drill out. Hearing results for patients with no bone growth were similar to hearing results for nonmeningitic patients; 75% had open-set speech recognition. Performance among patients with total drill out was poor because it was limited to detection and pattern perception of speech, and no patients had open-set speech recognition. Results for patients with partial drill out were similar to results in patients with no bone growth.
In light of the possibility of severe ossification, the timing of cochlear implantation may be an important determinant of successful cochlear implantation; however, timing for cochlear implantation after meningitis remains controversial. For more than 3 years, Brookhouser et al monitored 64 children with hearing loss associated with meningitis.[32] Of the children, 85% were found to have had a stable loss, whereas the others had changes in their auditory thresholds. This finding raised a valid concern regarding test reliability issues in young children. A later study documented a delayed benefit from hearing aid use 16-25 months after the development of profound deafness in 3 postmeningitic children. A gradual improvement in aided hearing thresholds was noted; therefore, some argued that cochlear implantation should be delayed at least 1 year.
Novak et al challenged this notion of a minimum waiting period in their study of the implication of cochlear implantation subsequent to labyrinthitis ossificans (LO) that was associated with meningitis.[13] This study noted radiographic evidence of cochlear ossification as early as 2 months after the onset of bacterial meningitis. Novak et al proceeded with early implantation to optimize electrode insertion, emphasizing that the development of severe ossification precludes the possibility of hearing recovery. The problem with this approach is that many children will be implanted who otherwise, after a sufficient hearing aid trial, would be determined to benefit quite adequately from the hearing aid alone.
Novak et al proposed guidelines in evaluating candidates for cochlear implantation. Conduct high-resolution CT scans of the cochlea in all patients who have profound bilateral hearing loss associated with meningitis. Perform CT scans 1-2 months after the onset of hearing loss. If early signs of ossification are suspected, and/or no evidence of hearing recovery is identified, repeat scans in 1-2 months. If radiographic evidence of bilateral intracochlear fibrosis or osteoneogenesis is identified on the second scan, and the child and family otherwise are satisfactory implant candidates, then undertake implantation as soon as possible. Screening with MRI studies may provide a more sensitive test for early fibrosis prior to calcification as was discussed above (see Imaging Studies).
Hassepass et al studied the outcome in 3 patients who had cochlear implants with unilateral hearing loss. The results showed moderate-to-high benefits in 2 cases and no benefit in the third. They concluded that in these cases cochlear implantation should be performed before signs of obliteration are evident.[33]
The goals of pharmacotherapy are to eradicate the infection, prevent complications, and reduce morbidity.
Clinical Context: Third-generation cephalosporin with broad-spectrum, gram-negative activity, including pseudomonas; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins, which, in turn, inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell wall synthesis, thus inhibiting cell wall biosynthesis. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
For excellent patient education resources, visit eMedicineHealth's Ear, Nose, and Throat Center; Brain and Nervous System Center; and Children's Health Center. Also, see eMedicineHealth's patient education articles Labyrinthitis, Meningitis in Children, and Meningitis in Adults.