Hilary A. Brodie

Role of tumor necrosis factor-α in sensorineural hearing loss after bacterial meningitis

Hypothesis: Blockade of tumor necrosis factor-α with tumor necrosis factor-α antibody will reduce the extent of cochlear injury and hearing loss associated with Streptococcus pneumoniae meningitis. Background: Inflammatory mediators play a significant role in the morbidity associated with bacterial meningitis, including hearing loss and labyrinthitis ossificans. Previous studies have shown the attenuation of hearing loss by the nonspecific blockade of such pathways. Methods: Fifty Mongolian gerbils were divided into four groups. Auditory brainstem response testing was conducted to measure hearing thresholds. Streptococcus pneumoniae meningitis was induced in Groups 1 and 2. Group 2 was then given a single intraperitoneal injection of tumor necrosis factor-α antibody, whereas Group 1 received phosphate-buffered saline. Uninfected animals in Groups 3 and 4 were implanted with osmotic pumps that delivered a continuous 8-day intrathecal flow of either tumor necrosis factor-α (Group 4) or phosphate-buffered saline (Group 3). After 6 weeks, auditory brainstem response testing was repeated. The cochleas were harvested and analyzed histomorphometrically. Results: Group 2 animals with Streptococcus pneumoniae meningitis that also received tumor necrosis factor-α antibody developed significantly less hearing loss than Group 1 animals with meningitis alone. The decrease in the average threshold at 4, 8, 16, and 32 kHz was 31, 30, 25, and 28 dB sound pressure level, respectively (p < 0.0092 for each). Furthermore, histomorphometric analysis showed significantly less damage to the organ of Corti, spiral ganglion, spiral ligament, and stria vascularis in Group 2. Conversely, tumor necrosis factor-α induced meningitis animals (Group 3) showed increased hearing loss compared with phosphate-buffered saline controls (Group 4), with p < 0.0001 at all frequencies. Conclusion: Tumor necrosis factor-α plays an important role in cochlear injury after bacterial meningitis. Blockade of tumor necrosis factor-α reduces postmeningitic hearing loss and cochlear injury. Induction of meningitis with intrathecal tumor necrosis factor-α also resulted in hearing loss and cochlear injury similar to bacterial meningitis.

Location and timing of initial osteoid deposition in postmeningitic labyrinthitis ossificans determined by multiple fluorescent labels

Objectives/Hypothesis Variable amounts of fibrosis and neo‐ossification fill the cochlea following bacterial meningitis. The purpose of the study was to delineate the timing and location of initial ossification following pneumococcal meningitis, as well as subsequent remodeling and resorption, over the 3‐month period after infection.

Chronology of labyrinthitis ossificans induced by Streptococcus pneumoniae meningitis.

Objective: Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear and vestibular lumen as an end‐stage sequelae to various pathologies. This study was designed to establish the sequence of events and chronology of the osteoneogenesis and calcification. Study Design: A prospective randomized double‐blind study. Methods: By using serial application of different colored fluorochromes, which deposit in newly forming bone, the timing of bone deposition and bone remodeling can be established. Labyrinthitis ossificans was induced in she groups (n = 5) of gerbils by an intrathecal injection of live Streptococcus pneumoniae. Group 1 received no fluorochrome labels, group 2 received one label, group 3 received three labels, and groups 4, 5, and 6 received four labels. The temporal bones were harvested after 2 weeks (group 1), 1 month (group 2), 3 months (group 3), 4 months (group 4), 6 months (group 5), and 12 months (group 6). Results: Sixteen of the 25 animals that received labels developed ossification, demonstrated with fluorescent microscopy. In the animals that developed labyrinthitis ossificans, newly formed disorganized bone began calcifying as early as 3 weeks (label 1) after S pneumoniae injection. Osteoneogenesis continued as evidenced by the presence of the other labels when first applied at 6 weeks (label 2), and 10 weeks (label 3). Ossification, calcification, and remodeling proceeded through a 12‐month course, wherein a reduction of labels was present at 6 months and total disappearance by 12 months. Conclusions: The use of fluorescent stains in this animal model provides a means to establish a timeline of the ossification seen in labyrinthitis ossificans. Key Words: Ossified cochlea, labyrinthitis, deafness, cochlear implant, meningitis.

Induction of labyrinthitis ossificans after pneumococcal meningitis: An animal model ☆ ☆☆ ★ ★★

Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologic conditions, resulting in labyrinthitis ossificans. The pathologic mechanisms of this disease remain poorly understood. To better study the sequence of events and contributing mechanisms involved in labyrinthitis ossificans, an animal model was developed. Three groups of Mongolian gerbils received either an intralabyrinthine injection of normal saline solution (group 1) or Streptococcus pneumoniae polysaccharide capsule antigens (groups 2 and 3). The temporal bones were harvested after 3 months and serially sectioned. None of the eight control animals (group 1), which received intralabyrinthine injections of normal saline solution had any histologic changes in their temporal bones. Nine of the surviving 19 animals in groups 2 and 3 had fibrosis or evidence of early ossification. A fourth group of Mongolian gerbils received two intrathecal injections of live S. pneumoniae organisms. The temporal bones were harvested after 3 months and serially sectioned. Fourteen of the surviving 15 animals had fibrosis or ossification or both. This animal model will provide a method for study of the mechanisms of labyrinthitis ossificans.

Choristoma of the middle ear: a component of a new syndrome?

Case Report Salivary choristoma of the middle ear is a rare entity. The authors report the 26th known case, which is unique in several respects: the patient had abnormalities of the first and second branchial arches, as well as the otic capsule and facial nerve in ways not yet reported. Our patient presented with bilateral preauricular pits, conchal bands, an ipsilateral facial palsy, and bilateral Mondini-type deformities. A review of the literature revealed salivary choristomas of the middle ear to be frequently associated with branchial arch abnormalities, most commonly the second, as well as abnormalities of the facial nerve. Review of the Literature All 25 cases were reviewed and the results reported with respect to clinical presentation, associated abnormalities, operative findings, and hearing results. It has been proposed that choristoma of the middle ear may represent a component of a syndrome along with unilateral hearing loss, abnormalities of the incus and/or stapes, and anomalies of the facial nerve. Conclusion Eighty-six percent of the reported patients with choristoma have three or four of the four criteria listed to designate middle ear salivary choristoma as part of a syndrome. In the remaining four patients, all of the structures were not assessed.

The Effects of Superoxide Dismutase in Gerbils with Bacterial Meningitis

BACKGROUND: Inflammatory products, such as oxygen radicals generated during the course of bacterial meningitis, can damage nerve endings, hair cells, and/or supporting cells in the cochlea. Superoxide dismutase (SOD), an O2-scavenger, has been shown to play an important role in the protection against radical toxicity in various animal experiments. OBJECTIVE: To study the antioxidant effects of SOD on the inflammatory response of gerbils with bacterial meningitis. STUDY DESIGN: Meningitis was induced in three groups of 10 gerbils by intrathecal (IT) injection of Streptococcus pneumoniae into the cisterna magna. Group 1 received IT SOD, group 2 received intramuscular (IM) SOD, and group 3, the control group, received IM normal saline. Histologic data and auditory brainstem responses (ABR) were obtained from each gerbil. RESULTS: Fibrosis and/or neo-ossification were near absent in the IT SOD group and significantly less fibrosis occurred in the IM group (IT vs. IM: P = 0.010; IT vs. control group: P = 0.001). The amount of surviving spiral ganglion cells correlated inversely with the extent of fibrosis (r = −0.753, P < 0.00001). CONCLUSIONS: IT injection of SOD significantly reduced cochlear fibrosis and neo-ossification, reduced the spiral ganglion cell loss, and decreased damage of the cochlear components following bacterial meningitis.

Assessing stapes piston position using computed tomography: a cadaveric study.

Hypothesis: Temporal bone computed tomographic (CT) scanning in the postoperative stapedotomy patient is inaccurate in assessing stapes piston position within the vestibule. Background: Poststapedotomy patients that have persistent vertigo may undergo CT scanning to assess the position of the stapes piston within the vestibule to rule out overly deep insertion. Vertigo is a recognized complication of the deep piston, and CT evaluation is often recommended. The accuracy of CT scan in this setting is unestablished. Methods: Stapedotomy was performed on 12 cadaver ears, and stainless steel McGee pistons were placed. The cadaver heads were then scanned using a fine-cut temporal bone protocol. Temporal bone dissection was performed with microscopic measurement of the piston depth in the vestibule. These values were compared with depth of intravestibular penetration measured on CT scan by 4 independent measurements. Results: The intravestibular penetration as assessed by computed tomography was consistently greater than the value found on cadaveric anatomic dissection. The radiographic bias was greater when piston location within the vestibule was shallower. The axial CT scan measurement was 0.53 mm greater, on average, than the anatomic measurement. On average, the coronal CT measurement was 0.68 mm greater than the anatomic measurement. The degree of overestimation of penetration, however, was highly inconsistent. Conclusion: Standard temporal bone CT scan is neither an accurate nor precise examination of stapes piston depth within the vestibule. We found that CT measurement consistently overstated intravestibular piston depth. Computed tomography is not a useful study in the evaluation of piston depth for poststapedectomy vertigo and is of limited value in this setting.

The possible role of immunologic injury in the dysplastic bony lesion in LP/J mice

An immunohistologic study was performed on temporal bones from 30 LP/J mice and 17 CBA/J mice to assess the role of immunologic injury in the pathogenesis of dysplastic bony lesions in LP/J mice. Temporal bones were harvested from animals aged 2 to 31 months to evaluate the progression of the disease. As early as 2 months of age, before the onset of bony lesions, the tympanic cavities frequently contained small effusions coating the ossicles and otic capsules that were demonstrated to contain immunoglobulins and pockets of macrophages. Later in the course of the disease, bony lesions grossly and histologically similar to human otosclerosis developed, which stained for immunoglobulins. No similar bony lesions, effusions, cellular infiltrates, or staining for immunoglobulins was detected in the control animals, even in the presence of acute otitis media. This study suggests a role of immunologic injury in the pathogenesis of dysplastic bony lesions in LP/J mice.

VENOUS CHANNELS OF THE PETROUS APEX : THEIR PRESENCE AND CLINICAL IMPORTANCE

A methyl methacrylate casting technique was used to make detailed casts of the intracerebral venous system of four human cadaver specimens. Seven of the eight petrous apices studied were diploeic (n = 5), or pneumatic (n = 2) and had venules coursing in the anterior petrous apex. These venules form conduits connecting the cavernous to the inferior petrosal sinus or the jugular bulb and have not been previously described. In addition to the air cell system of the petrous apex, these venules may represent pathways for the spread of infection and the development of petrous apicitis, Gradenigos syndrome, and the rare otogenic cavernous sinus thrombophlebitis. Their presence also may help explain the location of cholesterol granulomas, which afflict this area of the skull base.

Effects of Depletion of Complement in the Development of Labyrinthitis Ossificans

Hypothesis: Labyrinthitis ossificans results in part from the intense inflammatory response to Streptococcus pneumoniae cell wall components. Depletion of complement in Mongolian gerbils following induction of meningitis will reduce the degree of inflammation and subsequent cochlear fibrosis.