Otopathologic Analysis of Patterns of Postmeningitis Labyrinthitis Ossificans.

OBJECTIVE: Labyrinthitis ossificans (LO) may occur following meningitis and, in cases where cochlear implantation is indicated, complicate electrode insertion. LO is critical to identify for successful cochlear implantation, and histopathology is more sensitive than imaging for identification of LO. Herein we utilize otopathologic techniques to study the timing and location of intracochlear tissue formation following meningitic labyrinthitis (ML). STUDY DESIGN: Retrospective review. SETTING: Academic institution. METHODS: Temporal bone specimens with a history of bacterial ML were histologically evaluated. The location and extent of intracochlear tissue formation within the scala tympani (ST) and scala vestibuli (SV) were graded, and spiral ganglion neurons were counted. RESULTS: Fifty-one temporal bones were identified: 32 with no intracochlear tissue formation, 9 with fibrosis alone, and 10 with LO. Fibrosis was identified as early as 1.5 weeks after ML, while ossification was found only in specimens that survived multiple years after ML. All LO cases showed ossification of the ST at the round window membrane (RWM) with continuous extension throughout the basal turn. Extent of SV ossification correlated with that in the ST but showed frequent isolated distal involvement of the cochlea. Spiral ganglion neuron counts were lower than those in age-matched controls. CONCLUSION: In this human temporal bone study, we found that postmeningitic LO results in ossification at the RWM with continuous extension into the ST of the basal turn and variable involvement of the SV. Identification of a patent basal turn beyond RWM ossification of the ST should permit full electrode insertion. LEVEL OF EVIDENCE: Retrospective review.

Otomycosis With Tympanic Membrane Perforation: A Review of the Literature.

OBJECTIVE: The purpose of the present study was to assess the rate of tympanic membrane perforation in patients with otomycosis and to discuss the literature regarding the difficulties in managing this condition. DATA SOURCES: Literature review from 1999 to 2019, Web of Science, PubMed, and Medline. STUDY SELECTION: We searched for eligible articles concerning the clinical entity of tympanic membrane perforation secondary to otomycosis. Case series and clinical trials were the types of articles included for this review. DATA EXTRACTION: All the articles described in the study selection were used for this review. DATA SYNTHESIS: Statistical techniques were not used. CONCLUSION: Based on the available literature, it seems that tympanic membrane perforation secondary to otomycosis is not uncommon. The presence of this complication is associated with 2 problems: Antimycotic solutions are irritant to middle ear and may be ototoxic to the cochlea. Although most cases of fungus caused tympanic membrane (TM) perforation resolve with proper medical treatment, in a few patients a tympanoplasty may be required.

Adjunctive N-acetyl-L-cysteine in treatment of murine pneumococcal meningitis.

Despite antibiotic therapy, acute and long-term complications are still frequent in pneumococcal meningitis. One important trigger of these complications is oxidative stress, and adjunctive antioxidant treatment with N-acetyl-l-cysteine was suggested to be protective in experimental pneumococcal meningitis. However, studies of effects on neurological long-term sequelae are limited. Here, we investigated the impact of adjunctive N-acetyl-l-cysteine on long-term neurological deficits in a mouse model of meningitis. C57BL/6 mice were intracisternally infected with Streptococcus pneumoniae. Eighteen hours after infection, mice were treated with a combination of ceftriaxone and placebo or ceftriaxone and N-acetyl-l-cysteine, respectively. Two weeks after infection, neurologic deficits were assessed using a clinical score, an open field test (explorative activity), a t-maze test (memory function), and auditory brain stem responses (hearing loss). Furthermore, cochlear histomorphological correlates of hearing loss were assessed. Adjunctive N-acetyl-l-cysteine reduced hearing loss after pneumococcal meningitis, but the effect was minor. There was no significant benefit of adjunctive N-acetyl-l-cysteine treatment in regard to other long-term complications of pneumococcal meningitis. Cochlear morphological correlates of meningitis-associated hearing loss were not reduced by adjunctive N-acetyl-l-cysteine. In conclusion, adjunctive therapy with N-acetyl-l-cysteine at a dosage of 300 mg/kg of body weight intraperitoneally for 4 days reduced hearing loss but not other neurologic deficits after pneumococcal meningitis in mice. These results make a clinical therapeutic benefit of N-acetyl-l-cysteine in the treatment of patients with pneumococcal meningitis questionable.

Pneumococcal meningitis post cochlear implantation: development of an animal model in the guinea pig.

In 2002 an increased number of cochlear implant related meningitis cases was reported by the U. S. Food and Drug Administration (FDA). The most commonly identified causative agent was Streptococcus pneumoniae. Although most cases of meningitis were related to a special electrode design, the risk for post-operative pneumococcal meningitis might nonetheless be enhanced by opening of the cochlea during implantation. In the present study, a threshold model for middle ear inoculation of S. pneumoniae was established in the guinea pig after cochlear implantation to assess the post-operative risk of meningitis. Guinea pigs were implanted unilaterally with a silicone cochlear implant electrode dummy. Five weeks after implantation, animals were challenged via the middle ear with a clinically relevant strain of S. pneumoniae and monitored over a period of five days for signs of meningitis. Meningitis was confirmed by clinical outcome in the animals, histological investigation of brains, as well as by pleocytosis and presence of bacteria in cerebrospinal fluid (CSF). By inoculation of varying numbers of bacteria (between 1 × 10(4) and 1 × 10(9) CFU/ml in 10 µl), a threshold model was established. The attack rate, pattern and onset of meningitis depended on number of inoculated bacteria. An increased meningitis rate in different experimental groups shows that greater bacterial burden leads to an increased attack rate after intratympanal inoculation. The established animal model provides a potential tool to assess the meningitis risk after cochlear implantation. Its implementation in future studies will allow the investigation of existing and newly developed prostheses for postoperatively infection risk.

Otologic safety of manuka honey.

OBJECTIVE: To investigate the possible ototoxic effects of a 50% concentration of manuka honey in a chinchilla animal model. STUDY DESIGN: A prospective, controlled animal study. SETTING: The Research Institute of the Montreal Children's Hospital, McGill University Health Centre. SUBJECTS AND METHODS: Eight animals had myringotomy incisions in both ears. One ear was randomly assigned to receive the 50% manuka honey solution. The contralateral ear received saline and served as the control ear. OUTCOME MEASURES: Auditory brainstem evoked responses (ABRs) were measured bilaterally for a wide range of frequencies (between 8 and 25 kHz) before and 2 weeks after transtympanic manuka honey and saline application. The animals were sacrificed, and all cochleae were dissected out and processed for light and scanning electron microscopy (SEM). RESULTS: The measured ABR thresholds after the application of 50% concentration of manuka honey revealed severe ototoxicity in all honey-exposed ears. This was accompanied by gross physical changes and histologic evidence of hair cell toxicity on SEM and light microscopy. The control ears remained unchanged during the period of the experiment. CONCLUSION: Although 50% concentration of manuka honey is the proven concentration to have bactericidal properties against biofilms of Pseudomonas aeruginosa and Staphylococcus aureus, this concentration appeared to have caused severe or intense inflammatory changes that produced facial paralysis, vestibulotoxicity, and hearing loss.

Experimental studies of pneumococcal meningitis.

This thesis summarizes experimental meningitis research conducted at Statens Serum Institut in collaboration with the Copenhagen HIV programme and the Danish Research Centre for Magnetic Resonance between 2001 and 2007. Previous experimental studies had shown that the host inflammatory response in invasive infections contributed significantly to an extremely poor outcome despite initiation of efficient antimicrobial chemotherapy. Consequently, we aimed to investigate and clarify how the course of disease in pneumococcal meningitis was modulated by local meningeal inflammation and concomitant systemic infection and inflammation. Experimental studies were based on the development of a rat model of pneumococcal meningitis, refined and optimized to closely resemble the human disease, mimicking disease severity, outcome, focal- and global brain injury and brain pathophysiology. These endpoints were evaluated by the development of a clinical score system, definition of outcomes and measurement of hearing loss by otoacoustic emission. The investigation of in-vitro and in-vivo brain pathology with histology and MRI revealed an injury pattern similar to that found clinically. Additionally, MRI enabled the study of parameters closely related to the cerebral pathophysiology of meningitis (brain oedema, blood brain barrier (BBB) permeability, focal brain injury and hydrocephalus). Modulation of the inflammatory host response was achieved by initiation of treatment prior to infection: 1) G-CSF treatment increased the peripheral availability of leukocytes, 2) Selectin blocker fucoidin attenuated meningeal leukocyte accumulation and 3) A serotype specific Ab augmented systemic pneumococcal phagocytosis. The studies revealed a dual role of the inflammatory response in pneumococcal meningitis. Whilst focal brain injury appeared to result from local meningeal infectious processes, clinical disease severity and outcome appeared determined by systemic infection. Furthermore systemic disease contributed significantly to BBB permeability and brain ventricle expansion. Ventricle expansion was also associated with clinical appearance. An augmented systemic host response limited pneumococcal bacteraemia and protected from fatal outcome, but did not reduce occurrence of focal brain injury. Thus, our findings suggest that meningitis sequelae arise from local disease complications whereas fatal outcome is accelerated by systemic infection. Understanding of the relationship and interplay between septicaemia, intracranial pressure, ventricle expansion and brain edema could help optimize the treatment of these disease complications by, for example, improved systemic infection control. New therapeutic approaches to improve survival and neurological outcome from pneumococcal meningitis may be achieved through identification of the pathogen factors that initiate and prolong extensive systemic and local inflammation. Investigation of genomic differences and protein expression between pneumococcal serotypes or between identical serotypes with different virulence are considered crucial to this progress. Future progress may also be achieved by disease prevention with pneumococcal vaccines. Randomized trials of treatment strategies including bacteriostatic agents, antioxidants or more specific anti-inflammatory agents are realistic possibilities in the near future.

[Biomaterials in cochlear implants]. / Biomaterialien bei Cochlea-Implantaten.

Cochlear implants (CI) represent the "gold standard" for the treatment of congenitally deaf children and postlingually deafened adults. Thus, cochlear implantation is a success story of new bionic prosthesis development. Owing to routine application of cochlear implants in adults but also in very young children (below the age of one), high demands are placed on the implants. This is especially true for biocompatibility aspects of surface materials of implant parts which are in contact with the human body. In addition, there are various mechanical requirements which certain components of the implants must fulfil, such as flexibility of the electrode array and mechanical resistance of the implant housing. Due to the close contact of the implant to the middle ear mucosa and because the electrode array is positioned in the perilymphatic space via cochleostomy, there is a potential risk of bacterial transferral along the electrode array into the cochlea. Various requirements that have to be fulfilled by cochlear implants, such as biocompatibility, electrode micromechanics, and although a very high level of technical standards has been carried out there is still demand for the improvement of implants as well as of the materials used for manufacturing, ultimately leading to increased implant performance. General considerations of material aspects related to cochlear implants as well as potential future perspectives of implant development will be discussed.

MyD88-dependent immune response contributes to hearing loss in experimental pneumococcal meningitis.

Hearing loss is one of the most common sequelae in survivors of pneumococcal meningitis, affecting up to 26% of them. Here, we established the first mouse model of meningitis-associated hearing loss and investigated the role played by the Toll-like receptor-associated adapter molecule MyD88. C57BL/6 mice were infected intracisternally by Streptococcus pneumoniae. By use of audiometry and histological analysis, cochleae were assessed in uninfected control mice during the acute stage and after recovery. MyD88-deficient mice were analyzed 24 h after infection. Wild-type mice lost hearing capacity to a significant degree, which was accompanied by a granulocytic cochlear inflammation. After recovery, hearing loss was still evident, and spiral ganglion neuronal loss, hair cell damage, and fibrocytic occlusion of the cochlea were observed. In contrast, mice lacking MyD88 developed significantly less hearing loss and had diminished cochlear inflammation. Our results strongly suggest a proinflammatory role for MyD88 in the initiation of the inflammatory response during pneumococcal meningitis-associated labyrinthitis.

Doxycycline reduces mortality and injury to the brain and cochlea in experimental pneumococcal meningitis.

Bacterial meningitis is characterized by an inflammatory reaction to the invading pathogens that can ultimately lead to sensorineural hearing loss, permanent brain injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor alpha-converting enzyme (TACE) are key mediators that promote inflammation, blood-brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline is a clinically used antibiotic with anti-inflammatory effects that lead to reduced cytokine release and the inhibition of MMPs. Here, doxycycline inhibited TACE with a 50% inhibitory dose of 74 microM in vitro and reduced the amount of tumor necrosis factor alpha released into the cerebrospinal fluid by 90% in vivo. In an infant rat model of pneumococcal meningitis, a single dose of doxycycline (30 mg/kg) given as adjuvant therapy in addition to ceftriaxone 18 h after infection significantly reduced the mortality, the blood-brain barrier disruption, and the extent of cortical brain injury. Adjuvant doxycycline (30 mg/kg given subcutaneously once daily for 4 days) also attenuated hearing loss, as assessed by auditory brainstem response audiometry, and neuronal death in the cochlear spiral ganglion at 3 weeks after infection. Thus, doxycycline, probably as a result of its anti-inflammatory properties, had broad beneficial effects in the brain and the cochlea and improved survival in this model of pneumococcal meningitis in infant rats.

[Inner ear and subarachnoid spaces: relations and diseases]. / Oreille interne et espaces sous-arachnoïdiens.

The purpose of this article is to describe, with 5 clinical cases, the physiological communications between the inner ear and the subarachnoid spaces (SAS) and present the imaging features with regard to. Therefore we briefly illustrate abnormal communications between SAS and perilymphatic fluids in certain cochlear and internal acoustic meatus (IAM) malformations and their consequences. Imaging features may depict diffusion pathway of bacterial meningitis to membranous labyrinth via the cochlear aqueduct or via the IAM. Rarely, in some patients referred for cochleovestibular symptoms, imaging features may display skull base tumors involving the area of cochlear or vestibular aqueduct aperture. Therefore, in patients referred for cochleovestibular symptoms, MR and CT study should carefully scrutinise not only the IAM but also the aperture of the cochlear and the vestibular aqueducts and the cerebellopontine meninges.

Otitis interna is a frequent sequela to Streptococcus suis meningitis in pigs.

Twenty-eight histologically confirmed cases of porcine leptomeningitis were examined retrospectively, with focus on the pathology of the inner and middle ear, brain, and vestibulocochlear nerve. Tissues were evaluated by histology and immunohistochemistry for Streptococcus suis serotype 2 antigen, and the bacteriologic results were recorded. Exudative otitis interna was diagnosed in 20/28 pigs (71%). The lesions primarily affected the perilymphatic ducts, with consistent involvement of the scala tympani. Perineuritis of the vestibulocochlear nerve was seen in all but four of the ears affected with otitis interna. Immunohistochemically, S. suis serotype 2 antigen was demonstrated in the leptomeningeal, perineural, and labyrinthine exudates in 11 cases. Otitis media was diagnosed in 10/28 pigs (34%), but evidence of extension to the inner ear was not observed. The findings were highly similar to descriptions of meningogenic labyrinthitis in humans and in laboratory animal models. Otitis interna in pigs can also develop via the meningogenic route and is not always, as generally stated, tympanogenic.

Dexamethasone modifies the effect of Pseudomonas aeruginosa exotoxin A on hearing.

In the present study, the protective effect of dexamethasone was analysed following exposure of the cochlea to Pseudomonas aeruginosa Exotoxin A (PaExoA). Four groups of albino Sprague-Dawley rats were used. 20 microl saline was instilled through the tympanic membrane into the round window niche (group A, n = 4); 1 microg/20 microl dexamethasone sodium 21-phosphate (dexamethasone) solution was instilled (group B, n = 4); 1 microg/20 microl PaExoA solution was initially instilled followed 1 h later by 20 microl saline (group C, n = 6); and 1 microg/20 microl PaExoA solution was initially instilled followed 1 h later by 1 microg/20 microl dexamethasone solution (group D, n = 6). Frequency-specific (4, 8, 10, 12, 16 and 20 kHz) auditory brainstem responses (ABR) were used to ascertain the threshold prior to exposure and 1, 2, 3, and 5 days and 1 and 2 weeks afterwards. No threshold change was observed in groups A and B, whereas the animals in groups C and D showed some threshold elevation, that in D being smaller than that in C. There was a significant difference at the frequencies 12, 16 and 20 kHz, 2 and 5 days after exposure. The intensity-latency (I-L) curve showed that in group D the cochlear component almost disappeared at high frequency one week after exposure. Our results indicate that dexamethasone can modify the effect of PaExoA caused by non-specific inflammation.

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 six 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.

The influence of pneumococcal otitis media on the cochlear lateral wall.

The cochlear influence of otitis media was investigated in order to identify damaged regions causing cochlear malfunction. BALB/c mice were challenged with viable Streptococcus pneumoniae into the middle ear cavity and were killed 1 day to 1 month later for immunohistochemical analysis. Otitis media was induced in all of the animals, and some showed inflammatory cells in the cochlea. Although other changes were not obvious by hematoxylin and eosin staining, immunohistochemistry showed the presence of fibrinogen in the cochlea, mainly in the lower portion of the spiral ligament and in the spiral limbus. Immunostaining for connexin 26 was decreased in the spiral ligament, accompanied by marked fibrinogen staining. Immunostaining for sodium-potassium-adenosine triphosphatase in the stria vascularis and in the type II fibrocytes of the spiral ligament was not affected obviously. The presence of fibrinogen in the cochlea suggests disruption of the blood-labyrinth barrier caused by the middle ear inflammation. Changes in connexin 26 staining suggest the possibility that the spiral ligament could be among the regions responsible for the cochlear malfunction.

Oral immunization of rabbits against Pasteurella multocida with an alginate microsphere delivery system.

Oral delivery of microencapsulated antigens is a potential means to vaccinate rabbits against Pasteurella multocida, a common bacterial pathogen. Groups of five rabbits were dosed orally on days 0, 7, and 14 with alginate microspheres prepared to contain no added protein, 5 mg of a potassium thiocyanate extract of P. multocida (PTE), or 5 mg of PTE with 200 micrograms of cholera toxin (CT). In addition, groups were dosed orally with 5 mg of soluble PTE with or without 200 micrograms CT, intranasally (IN) with 1 mg of soluble PTE, or with saline. Serum and nasal lavage samples collected prior to initial immunization and 10, 16, and 21 days later were assayed by ELISA for anti-PTE IgG and IgA. Strong nasal lavage IgA and serum IgG activities were found in samples from rabbits immunized with PTE IN or orally when incorporated into microspheres. Addition of CT did not significantly enhance either response. To examine the development of protective immunity, groups were similarly immunized and challenge-exposed IN on day 16 with 10(6) CFU of P. multocida. One week later, rabbits were euthanized, and specimens from the lungs, nasopharynx, liver, and inner ear were cultured for P. multocida. Less severe infections of the lung and nasopharynx developed in rabbits immunized with PTE IN or orally in microspheres, with or without added CT. In addition, culture of liver and tympanic bullae samples from these rabbits yielded growth of P. multocida less frequently compared to other P. multocida-challenged rabbits. Coadministration of CT and PTE did not significantly improve protective immunity to challenge.

The cochlear lesion in experimental bacterial meningitis of the rabbit.

Sensorineural hearing loss was studied in a rabbit model of experimental bacterial meningitis using electrophysiological and ultrastructural techniques. Hearing impairment was monitored by auditory brain-stem evoked responses (ABERs) and concomitant structural lesions were identified by both transmission (TEM) and scanning (SEM) electron microscopy. Meningitis was induced by intra-cerebrospinal fluid injection of either Escherichia coli (strain 2073 and type K-12) or Haemophilus influenzae type b. Auditory loss of approximately equal to 10 dB occurred in all rabbits by about 10 hours post infection and progressed in severity until by 20 h following infection, hearing losses up to and > 60 dB were obtained. At levels of hearing loss < 20 dB ultrastructural damage to the organ of Corti was barely detectable. With greater levels of hearing loss, patchy structural damage to hair cells, synaptic nerve terminals, supporting cells and inner spiral sulcus cells and cells of the stria vascularis was clearly evident. Bacteria were found in scala tympani, the basilar membrane, the organ of Corti, scala media, the spiral ligament and at the margin of the stria vascularis. Evidence of bleeding was found in some cochleas; erythrocytes were found in scala tympani, scala media, amongst hair cells and beneath the tectorial membrane. The results show that hearing loss is associated with bacterial invasion and damage to the organ of Corti and that the cause of hearing loss is likely to result from multiple lesions within the cochlea. Lesions to sensory cells almost certainly will produce permanent hearing loss. Lesions to supporting cells, nerve terminals and to stria vascularis may well produce only temporary hearing loss.

Acute measles infection in the hamster cochlea.

Measles virus has been implicated in sudden sensorineural hearing loss (SNHL) in adults as well as in children. Furthermore, sensorineural hearing loss following live measles virus vaccination has been reported. As of yet, however, there has been only few reports on human temporal bone pathology due to measles, and on experimental animal models of measles infection. This study was undertaken to examine acute measles infection in adult hamster cochlea morphologically and immunohistochemically for precise understanding of this viral infection. Atrophy of the stria vascularis, loss of the organ of Corti, "rolled-up" tectorial membrane, and cell infiltration with a positive immunofluorescent reaction primarily within the scale media indicating endolymphatic labyrinthitis were the principal findings. These results were generally consistent with previous ones on human temporal bone pathology not only due to measles but also to SNHL. We consider measles virus to be one of the possible pathogens, even if low in frequency, causing profound and irreversible hearing loss, including SNHL. Completion of measles vaccination without complication and selective or mass revaccination may be necessary to prevent such hearing loss.

Use of poly-l-aspartic acid to inhibit aminoglycoside cochlear ototoxicity.

Gentamicin is an extremely effective antibiotic against a wide variety of organisms. However, its use is limited by its nephrotoxic and ototoxic effects. Recent studies in rats have shown that poly-l-aspartic acid (PAA) effectively blocks the nephrotoxic effects of the aminoglycosides and does not decrease the antibiotic effectiveness of gentamicin against those organisms tested. A controlled test was undertaken to evaluate the effect of PAA on cochlear ototoxicity. Test solutions were administered to four groups of guinea pigs for 10 days. Group 1, the controls, received distilled water, group 2 received gentamicin, group 3 received PAA, and group 4 received gentamicin plus PAA. Auditory brainstem response thresholds at 20, 16, 8, and 4 kHz were obtained before therapy, after completion of the 10-day course, and 21 days following the completion of therapy. Two-dimensional diffusion assays in human serum were performed to evaluate the effect of PAA on the antimicrobial activity. Histologic evaluation of the cochleae was performed at the conclusion of the experiment. Threshold shifts following 10 days of therapy were not statistically significant in group 4 compared to controls, while the gentamicin group (group 2) was significantly different for all frequencies tested. At 21 days following therapy, group 4 (PAA + gentamicin) maintained significance in the higher frequencies studied. Antimicrobial studies demonstrated that PAA has no effect on the antimicrobial activity of gentamicin and has no antimicrobial effect against Bacillus subtilis when used alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxic effects on hair cells of guinea pig cochlea produced by pneumolysin, the thiol activated toxin of Streptococcus pneumoniae.

The cytolytic toxin, pneumolysin, from the gram positive bacterium, Streptococcus pneumoniae, when perfused through the scala tympani of the guinea pig cochlea reduced the amplitude of both the compound action potential and the cochlear microphonic potential. When the surface of the organ of Corti was examined by scanning electron microscopy, both inner and outer hair cells and supporting cells were found to be damaged. Inner hair cells and outer hair cells of row 3 were the most susceptible to damage by pneumolysin, followed by row 2 and then by row 1 of the outer hair cells. Damage to hair cells included disruption and splaying of stereocilia, loss of stereocilia and complete dissolution of hair bundles. Apical surfaces of hair cells and supporting cells were torn, pitted and cratered with shrinkage and tearing of cell boundaries. Within the dose range perfused (0.05-1 micrograms/microliters in a 10 microliters aliquot), the magnitude of the physiological and anatomical lesions was concentration dependent. The cytotoxic effects of pneumolysin reported here may be clinically significant factors in deafness caused by meningitis and otitis media in humans.