AUTHOR AND EDITOR INFORMATION

Section 1 of 8  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 8  

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• Introduction
• Clinical
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• Treatment
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Background

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) 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.

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 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 LO.

Pathophysiology

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 (see Image 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.

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 1993, 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. 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. They divided the evolution of LO into 3 characteristic stages: acute, fibrous, and ossification (see Image 2). 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 (see Image 3).

Formation of osteoid with subsequent mineralization and remodeling obliterates the perilymphatic and endolymphatic spaces.Ossificationin 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 LO subsequent to Streptococcus pneumoniae–induced meningitis. 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. 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. 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. 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.

The phenomenon of 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.

Frequency

United States

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 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. 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 Causes). 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.

CLINICAL

Section 3 of 8  

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Causes

• The most common cause of LO is bacterial infection of the inner ear that results in suppurative labyrinthitis. Bacterial invasion of the labyrinth can occur via 3 routes: hematogenic spread through the cochlear vasculature, a sequela to otitis media that passes through the round window membrane, or meningogenic spread from the subarachnoid space in meningitis (see Picture 6).
• Based on data from 1995, the 3 most common organisms responsible for bacterial meningitis in the United States are H influenzae (0.2 cases per 100,000 population), S pneumoniae (1.1 cases per 100,000 population), and Neisseria meningitidis (0.6 cases per 100,000 population). With the success of conjugate vaccines in preventing invasive H influenzae type b (Hib) disease, S pneumoniae has become the leading cause of bacterial meningitis in the United States. Children younger than 1 year have the highest incidence of pneumococcal meningitis (approximately 10 cases per 100,000 population).
• Woolley et al performed a retrospective study of 432 patients with meningitis and determined that 59 (13.7%) developed hearing loss. Forty-six (78%) of these children with hearing loss had stable auditory thresholds over time, and 13 (22%) exhibited deterioration or fluctuation of acuity over time. The authors determined that significant predictors of future hearing loss included increased intercranial pressure (revealed with CT scan), male sex, low cerebrospinal fluid glucose levels, S pneumoniae as a causative organism, and the presence of nuchal rigidity.
• The cells and mechanisms responsible for ossification in LO are unknown; however, several hypotheses have been proposed.
• • In 1967, Paparella and Sugiura hypothesized that bone-lining cells of the cochlea are pluripotent mesenchymal stem cells that remain uncommitted until stimulated to differentiate into osteoblasts.
  • In 1985, Kotzias and Linthicum hypothesized that this type of bone originates from osteoblasts within the otic capsule. They suggested that ectopic bone forms on the endosteal layer after inflammatory insult, but the bone is not incorporated beyond the surface.
  • Additionally, pericytes associated with blood vessels that supply the modiolus and spiral ligament fibroblasts have been hypothesized as cells of origin.
  • In an antemortem analysis of LO in a human case report, metaplastic bone was reported to have formed within serofibrinous exudate; however, the cell of origin for the osteoneogenesis has not been identified. Because the new bone deposition occurs in continuity with endosteal bone, postmortem studies are not able to differentiate metaplastic bone from osteoplastic bone within the cochlea. The cells and mechanisms responsible for ossification in LO remain undefined.

WORKUP

Section 4 of 8  

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• Treatment
• Follow-up
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Imaging Studies

• Until recently, 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 (see Images 4-5).
• • In 1 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. 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 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 suggests high-resolution, fast spin-echo, T2-weighted MRI is clinically helpful in cochlear implant candidates. 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 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. However, the value of MRI in preoperative assessment of candidates for cochlear implantation is not universally accepted.

Histologic Findings

See Pathophysiology.

TREATMENT

Section 5 of 8  

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Medical Care

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. 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. Hartnick et al performed a retrospective study of 10 patients with pneumococcal meningitis who received cochlear implantation for bacterial meningitis–related deafness. 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 theincidence of hearing loss when administered early in the course of meningitis.

S pneumoniae infection carries the highest incidence of associated LO. The immunogenicity of the S pneumoniae cell wall has been implicated in likelihood of developing 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 LO in experimental animals. 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 theblood-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. 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. 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 reduced postmeningitic hearing loss and cochlear injury. They showed that induction of meningitis with intrathecal TNF-α also resulted in hearing loss and cochlear injury similar to bacterial meningitis. 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.

Surgical Care

The clinical significance of 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. 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 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. Gantz et al first reported radical cochleostomy for advanced 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. 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. Steenerson and Gary subsequently reported that 3 patients with LO who underwent implantation using the Gantz radicalcochleostomy had some benefit from the device. 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 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. Thirty-one percent have severe 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. 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 LO that was associated with meningitis. 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).

FOLLOW-UP

Section 6 of 8  

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Deterrence/Prevention

See Treatment.

Patient Education

For excellent patient education resources, visit eMedicine's Ear, Nose, and Throat Center; Brain and Nervous System Center; and Children's Health Center. Also, see eMedicine's patient education articles Labyrinthitis, Meningitis in Children, and Meningitis in Adults.

MULTIMEDIA

Section 7 of 8  

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Media file 1:  Fibrosis and ossification of the scala tympani are shown. F, fibrosis; O, osteoneogensis (hematoxylin and eosin stain).
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Media file 2:  Stages of ossification are shown. This histological specimen was obtained 3 months after induction of labyrinthitis. F, fibrosis; O, osteoid; C, calcospherite deposition (calcification); B, normal endochondral bone. (hematoxylin and eosin stain)
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Media file 3:  Ossification of the scala tympani is shown.
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Media file 4:  Labyrinthitis ossificans is depicted with right cochlea enhancement.
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Media type:  CT

Media file 5:  Labyrinthitis ossificans is shown on axial CT scan.
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Media file 6:  Labyrinthitis ossificans associated with meningitis is shown.
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Media type:  CT

REFERENCES

Section 8 of 8

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• Introduction
• Clinical
• Workup
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• References

• Aminpour S, Tinling SP, Brodie HA. Role of tumor necrosis factor-alpha in sensorineural hearing loss after bacterial meningitis. Otol Neurotol. Jul 2005;26(4):602-9. [Medline].
• Arriaga MA, Carrier D. MRI and clinical decisions in cochlear implantation. Am J Otol. Jul 1996;17(4):547-53. [Medline].
• Balkany T, Gantz B, Nadol JB Jr. Multichannel cochlear implants in partially ossified cochleae. Ann Otol Rhinol Laryngol Suppl. Sep-Oct 1988;135:3-7. [Medline].
• Benitez JT, Bouchard KR, Lane-Szopo D. Pathology of deafness and disequilibrium in head injury:a human temporal bone study. Am J Otol. Jan 1980;1(3):163-7. [Medline].
• Berlow SJ, Caldarelli DD, Matz GJ, et al. Bacterial meningitis and sensorineural hearing loss: a prospective investigation. Laryngoscope. Sep 1980;90(9):1445-52. [Medline].
• Bhatt S, Halpin C, Hsu W, et al. Hearing loss and pneumococcal meningitis: an animal model. Laryngoscope. Dec 1991;101(12 Pt 1):1285-92. [Medline].
• Blamey P, Arndt P, Bergeron F, et al. Factors affecting auditory performance of postlinguistically deaf adults using cochlear implants. Audiol Neurootol. Sep-Oct 1996;1(5):293-306. [Medline].
• Brodie HA, Thompson TC, Vassilian L, et al. Induction of labyrinthitis ossificans after pneumococcal meningitis: an animal model. Otolaryngol Head Neck Surg. Jan 1998;118(1):15-21. [Medline].
• Brookhouser PE, Auslander MC, Meskan ME. The pattern and stability of postmeningitic hearing loss in children. Laryngoscope. Sep 1988;98(9):940-8. [Medline].
• Brookhouser PE, Auslander MC. Aided auditory thresholds in children with postmeningitic deafness. Laryngoscope. Aug 1989;99(8 Pt 1):800-8. [Medline].
• Chen MC, Harris JP, Keithley EM. Immunohistochemical analysis of proliferating cells in a sterile labyrinthitis animal model. Laryngoscope. May 1998;108(5):651-6. [Medline].
• Chole RA, Tinling SP. Incomplete coverage of mammalian bone matrix by lining cells. Ann Otol Rhinol Laryngol. Jul 1993;102(7):543-50. [Medline].
• Clopton BM, Spelman FA, Miller JM. Estimates of essential neural elements for stimulation through a cochlear prosthesis. Ann Otol Rhinol Laryngol Suppl. Mar-Apr 1980;89(2 Pt 2):5-7. [Medline].
• Cohen NL, Hoffman R, Waltzman S. Electrode insertion in the totally obstructed cochlea. Presented at: Third Annual Cochlear Implant Conference. 1993;Innsbruk, Austria.
• Crowe SJ. Pathologic changes in meningitis of the internal ear. Arch Otolaryngol. 1930;11(5):537-568.
• DeSautel MG, Brodie HA. Effects of depletion of complement in the development of labyrinthitis ossificans. Laryngoscope. Oct 1999;109(10):1674-8. [Medline].
• Dorman MF, Loizou PC, Rainey D. Speech intelligibility as a function of the number of channels of stimulation for signal processors using sine-wave and noise-band outputs. J Acoust Soc Am. Oct 1997;102(4):2403-11. [Medline].
• Druss JG. Labyrinthitis secondary to meningococcic meningitis: a clinical and histopathologic study. Arch Otolaryngol. 1936;24:19-28.
• Eisenberg LS, Luxford WM, Becker TS, et al. Electrical stimulation of the auditory system in children deafened by meningitis. Otolaryngol Head Neck Surg. Dec 1984;92(6):700-5. [Medline].
• Finitzo-Hieber T, Simhadri R, Hieber JP. Abnormalities of the auditory brainstem response in post-meningitic infants and children. Int J Pediatr Otorhinolaryngol. Dec 1981;3(4):275-86. [Medline].
• Fredrickson JM, Griffith AW, Lindsay JR. Transverse fracture of the temporal bone: a clinical and histopathologic study. Arch Otolaryngol. 1963;78:770-784.
• Friedmann I, Arnold W. Pathology of the Ear. New York, NY: Churchill Livingstone;1993:752.
• Gantz BJ, McCabe BF, Tyler RS. Use of multichannel cochlear implants in obstructed and obliterated cochleas. Otolaryngol Head Neck Surg. Jan 1988;98(1):72-81. [Medline].
• Ge NN, Brodie SA, Tinling SP. The effects of superoxide dismutase in gerbils with bacterial meningitis. Otolaryngol Head Neck Surg. Nov 2004;131(5):563-72. [Medline].
• Green JD Jr, Marion MS, Hinojosa R. Labyrinthitis ossificans: histopathologic consideration for cochlear implantation. Otolaryngol Head Neck Surg. Mar 1991;104(3):320-6. [Medline].
• Hagens EW. Pathology of the inner ear in a case of deafness from epidemic cerebrospinal meningitis. Ann Otol Rhinol Laryngol. 1940;49:168-176.
• Hartnick CJ, Kim HH, Kim HY, et al. Preventing labyrinthitis ossificans: the role of steroids. Arch Otolaryngol Head Neck Surg. Feb 2001;127(2):180-3. [Medline].
• Igarashi M, Saito R, Alford BR, et al. Temporal bone findings in pneumococcal meningitis. Arch Otolaryngol. Feb 1974;99(2):79-83. [Medline].
• Jackler RK, Luxford WM, Schindler RA, et al. Cochlear patency problems in cochlear implantation. Laryngoscope. Jul 1987;97(7 Pt 1):801-5. [Medline].
• Johnson MH, Hasenstab MS, Seicshnaydre MA, Williams GH. CT of postmeningitic deafness: observations and predictive value for cochlear implants in children. AJNR Am J Neuroradiol. Jan 1995;16(1):103-9. [Medline].
• Kadurugamuwa JL, Hengstler B, Zak O. Effects of antiinflammatory drugs of arachidonic acid metabolites and cerebrospinal fluid proteins during infectious pneumococcal meningitis in rabbits. Pediatr Infect Dis J. 1987;6:1153-4.
• Kawano A, Seldon HL, Pyman B, et al. Intracochlear factors contributing to psychophysical percepts following cochlear implantation: a case study. Ann Otol Rhinol Laryngol Suppl. Sep 1995;166:54-7. [Medline].
• Keane WM, Potsic WP, Rowe LD, et al. Meningitis and hearing loss in children. Arch Otolaryngol. Jan 1979;105(1):39-44. [Medline].
• Kimura R, Perlman HB. Arterial obstruction of the labyrinth. Part I. Cochlear changes. Part II. Vestibular changes. Ann Otol Rhinol Laryngol. 1958;67(1):5-24; 25-40.
• Kotzias SA, Linthicum FH Jr. Labyrinthine ossification: differences between two types of ectopic bone. Am J Otol. Nov 1985;6(6):490-4. [Medline].
• Lambert PR, Ruth RA, Hodges AV. Multichannel cochlear implant and electrically evoked auditory brainstem responses in a child with labyrinthitis ossificans. Laryngoscope. Jan 1991;101(1 Pt 1):14-9. [Medline].
• Lebel MH, Freij BJ, Syrogiannopoulos GA, et al. Dexamethasone therapy for bacterial meningitis. Results of two double- blind, placebo-controlled trials. N Engl J Med. Oct 13 1988;319(15):964-71. [Medline].
• Logan TA, Fraser JS. Labyrinthitis: a complication of middle ear suppuration: a clinical and pathologic study. J Laryngol Otol. 1928;43(609).
• Morgan BP, Gasque P. Expression of complement in the brain: role in health and disease. Immunol Today. Oct 1996;17(10):461-6. [Medline].
• Morgan WE, Coker NJ, Jenkins HA. Histopathology of temporal bone fractures: implications for cochlear implantation. Laryngoscope. Apr 1994;104(4):426-32. [Medline].
• Nabili V, Brodie HA, Neverov NI, et al. Chronology of labyrinthitis ossificans induced by Streptococcus pneumoniae meningitis. Laryngoscope. Jun 1999;109(6):931-5. [Medline].
• Nadol JB Jr, Hsu WC. Histopathologic correlation of spiral ganglion cell count and new bone formation in the cochlea following meningogenic labyrinthitis and deafness. Ann Otol Rhinol Laryngol. Sep 1991;100(9 Pt 1):712-6. [Medline].
• Nadol JB Jr. Hearing loss as a sequela of meningitis. Laryngoscope. May 1978;88(5):739-55. [Medline].
• Nager FR, Fraser JS. Bone formation in the scala tympani of otosclerotics. J Laryngol Otol. 1938;52:173-180.
• Novak MA, Fifer RC, Barkmeier JC, et al. Labyrinthine ossification after meningitis: its implications for cochlear implantation. Otolaryngol Head Neck Surg. Sep 1990;103(3):351-6. [Medline].
• Otte J, Schunknecht HF, Kerr AG. Ganglion cell populations in normal and pathological human cochleae. Implications for cochlear implantation. Laryngoscope. Aug 1978;88(8 Pt 1):1231-46. [Medline].
• Paparella MM, Sugiura S. The pathology of suppurative labyrinthitis. Ann Otol Rhinol Laryngol. Aug 1967;76(3):554-86. [Medline].
• Rarey KE, Bicknell JM, Davis LE. Intralabyrinthine osteogenesis in Cogan''s syndrome. Am J Otolaryngol. Nov-Dec 1986;7(6):387-90. [Medline].
• Rauch SD, Herrmann BS, Davis LA, Nadol JB. Nucleus 22 cochlear implantation results in postmeningitic deafness. Laryngoscope. Dec 1997;107(12 Pt 1):1606-9. [Medline].
• Richardson MP, Reid A, Williamson TJ, et al. Acute otitis media and otitis media with effusion in children with bacterial meningitis. J Laryngol Otol. Oct 1997;111(10):913-6. [Medline].
• Rodriguez AF, Kaplan SL, Hawkins EP, et al. Hematogenous pneumococcal meningitis in the infant rat: description of a model. J Infect Dis. Dec 1991;164(6):1207-9. [Medline].
• Rosenberg RA, Cohen NL, Reede DL. Radiographic imaging for the cochlear implant. Ann Otol Rhinol Laryngol. May-Jun 1987;96(3 Pt 1):300-4. [Medline].
• Rosenhall U, Nylen O, Lindberg J, et al. Auditory function after Haemophilus influenzae meningitis. Acta Otolaryngol. Mar-Apr 1978;85(3-4):243-7. [Medline].
• Schachern PA, Paparella MM, Hybertson R, et al. Bacterial tympanogenic labyrinthitis, meningitis, and sensorineural damage. Arch Otolaryngol Head Neck Surg. Jan 1992;118(1):53-7. [Medline].
• Schlech WF 3rd, Ward JI, Band JD, et al. Bacterial meningitis in the United States, 1978 through 1981. The National Bacterial Meningitis Surveillance Study. JAMA. Mar 22-29 1985;253(12):1749-54. [Medline].
• Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med. Oct 2 1997;337(14):970-6. [Medline].
• Schuknecht H. Pathology of the Ear. Philadelphia, Pa: Lea & Febiger;1993:672.
• Schwaber MK, Tarasidis NG. Labyrinthitis ossificans following post-traumatic hearing loss and vertigo: a case report with antemortem histopathology. Otolaryngol Head Neck Surg. Jan 1990;102(1):89-91. [Medline].
• Seicshnaydre MA, Johnson MH, Hasenstab MS, et al. Cochlear implants in children: reliability of computed tomography. Otolaryngol Head Neck Surg. Sep 1992;107(3):410-7. [Medline].
• Steenerson RL, Gary LB. Multichannel cochlear implantation in obliterated cochleas using the Gantz procedure. Laryngoscope. Sep 1994;104(9):1071-3. [Medline].
• Stutman HR, Marks MI. Bacterial meningitis in children: diagnosis and therapy. A review of recent developments. Clin Pediatr (Phila). Sep 1987;26(9):431-8. [Medline].
• Suga F, Lindsay JR. Labyrinthitis ossificans due to chronic otitis media. Ann Otol Rhinol Laryngol. Jan-Feb 1975;84(1 Pt 1):37-44. [Medline].
• Sugiura S, Paparella MM. The pathology of labyrinthine ossification. Laryngoscope. Nov 1967;77(11):1974-89. [Medline].
• Telian SA, Zimmerman-Phillips S, Kileny PR. Successful revision of failed cochlear implants in severe labyrinthitis ossificans. Am J Otol. Jan 1996;17(1):53-60. [Medline].
• Tinling SP, Colton J, Brodie HA. Location and timing of initial osteoid deposition in postmeningitic labyrinthitis ossificans determined by multiple fluorescent labels. Laryngoscope. Apr 2004;114(4):675-80. [Medline].
• Tuomanen E, Hengstler B, Rich R, et al. Nonsteroidal anti-inflammatory agents in the therapy for experimental pneumococcal meningitis. J Infect Dis. May 1987;155(5):985-90. [Medline].
• Vernon M. Meningitis and deafness: the problem, its physical, audiological, psychological, and educational manifestations in deaf children. Laryngoscope. Oct 1967;77(10):1856-74. [Medline].
• Ward PH. The histopathology of auditory and vestibular disorders in head trauma. Ann Otol Rhinol Laryngol. Apr 1969;78(2):227-38. [Medline].
• Wenger JD, Hightower AW, Facklam RR, et al. Bacterial meningitis in the United States, 1986: report of a multistate surveillance study. The Bacterial Meningitis Study Group. J Infect Dis. Dec 1990;162(6):1316-23. [Medline].
• Woolley AL, Kirk KA, Neumann AM, et al. Risk factors for hearing loss from meningitis in children: the Children's Hospital experience. Arch Otolaryngol Head Neck Surg. May 1999;125(5):509-14. [Medline].
• Yeung AH, Tinling SP, Brodie HA. Inhibition of post-meningitic cochlear injury with cerebrospinal fluid irrigation. Otolaryngol Head Neck Surg. Feb 2006;134(2):214-24. [Medline].
• Zimmermann CE, Burgess BJ, Nadol JB Jr. Patterns of degeneration in the human cochlear nerve. Hear Res. Oct 1995;90(1-2):192-201. [Medline].
• Zwahlen A, Nydegger UE, Vaudaux P, et al. Complement-mediated opsonic activity in normal and infected human cerebrospinal fluid: early response during bacterial meningitis. J Infect Dis. May 1982;145(5):635-46. [Medline].
• deSouza C, Paparella MM, Schachern P, et al. Pathology of labyrinthine ossification. J Laryngol Otol. Aug 1991;105(8):621-4. [Medline].

Article Last Updated: Aug 21, 2006