Labyrinthitis Ossificans Treatment & Management

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. ^[19] 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. ^[20] Hartnick et al performed a retrospective study of 10 patients with pneumococcal meningitis who received cochlear implantation for bacterial meningitis–related deafness. ^[21] 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. ^[22]

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. ^[23] 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. ^[24] 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. ^[25] 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. ^[26] 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. ^[27] 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. ^[28] 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. ^[29] 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. ^[30]

Steenerson and Gary subsequently reported that 3 patients with LO who underwent implantation using the Gantz radical cochleostomy had some benefit from the device. ^[31] 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. ^[32] 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. ^[33] 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. ^[14] 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).

A retrospective study by Maxwell et al of seven patients (eight ears) with intracochlear fibrosis indicated that the success of cochlear implantation is not reliant on the insertion technique, with improvement in pure-tone average having been comparable between patients who were treated with fibrosis removal and those in whom dilation was performed. With a styleted electrode used in most cases, owing to dense fibrosis, implants were fully inserted into all but one ear, this last having displayed partial ossification. Implantation followed meningitis/labyrinthitis by 1-4 months, and idiopathic sudden sensorineural hearing loss by 12-24 months. The least successful outcomes were associated with the longest times to surgery. ^[34]

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. ^[35]