Temporal Bone Pathology Secondary to Head Trauma-A Human Temporal Bone Study.

HYPOTHESIS/BACKGROUND: We hypothesize that following head trauma there is a difference in temporal bone (TB) pathology in cases with and without skull fracture. Although conductive, sensorineural, mixed hearing loss, and TB pathology following head trauma have been reported, to our knowledge, there are no studies that have compared the pathology of the TB in cases with and without skull fracture. METHODS: We analyzed 34 TBs from donors who had a history of head trauma (20 with skull fracture and 14 without fracture), and 25 age-matched controls without clinical or histological evidence of otologic disorders. We documented the presence and location of TB fracture, ossicular injury, and cochlear hemorrhage and evaluated the loss of spiral ganglion cells and sensory hair cells, damage to the stria vascularis, and the presence of endolymphatic hydrops. RESULTS: We found a significant loss of outer hair cells in the upper basal, lower, and upper middle turns of the cochlea (p = 0.009, =0.019, =0.040, respectively), a significant loss of spiral ganglion cells (p = 0.023), and cochlear hemorrhage predominantly in the basal turns secondary to head trauma. Interestingly, these findings were significantly observed in TBs from donors with a history of head trauma without skull fracture. CONCLUSION: The greatest damage was to the cochlear basal turn. Our findings suggest that head trauma may result in tonotopic high frequency sensorineural hearing loss. TBs from donors with skull fracture have less pathologic changes than those without.

Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement.

Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively). Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs. The disease can be divided into severe (Hurler syndrome) and attenuated (Hurler-Scheie, Scheie) forms. Currently approved treatments consist of enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). Patients with attenuated disease are often treated with ERT alone, while the recommended therapy for patients with Hurler syndrome consists of HSCT. While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. This review discusses these standard therapies and their impact on common disease manifestations in patients with MPS I. Where relevant, results of animal models of MPS I will be included. Finally, we highlight alternative and emerging treatments for the most common disease manifestations.

Quantitative assessment of cochlear and vestibular ganglion neurons in temporal bones with chronic otitis media.

PURPOSE: In this study, we aimed to determine whether or not COM leads to loss of spiral and Scarpa ganglion neurons. METHODS: From the human temporal bone (HTB) collection at the University of Minnesota we selected human temporal bones with COM, defined as the presence of clinically intractable tissue abnormalities in the middle ear (cholesteatoma, perforation of the eardrum, granulation tissue, fibrosis, tympanosclerosis, and cholesterol granuloma). We also selected HTBs from donors with no ear diseases as controls. We quantitatively analyzed the number of spiral and Scarpa ganglion cells and compared the results obtained in the control and study groups. RESULTS: In both COM and control groups we observed a significant negative correlation between age and number of both spiral (R = -0.632; P < 0.001; 95% CI - 0.766 to - 0.434) and Scarpa ganglion (R = - 0.404; P = 0.008; 95% CI - 0.636 to - 0.051) cells. We did not find any significant differences in the number of spiral ganglion cells (in total or per segment) or in the density of Scarpa ganglion cells (in each vestibular nerve or both) in the COM group as compared with controls (P > 0.05). CONCLUSIONS AND RELEVANCE: Our results did not demonstrate significant loss of cochlear or vestibular peripheral ganglion neuron loss in HTBs with COM as compared with controls.

Bilateral glomus tympanicum tumors: Human temporalbone study.

To describe human temporal bones with bilateral glomus tympanicum tumors. Patient is 83-year-old black female who no pulsatile tinnitus. The histopathologic characteristics of human temporal bones after death were setting Department of Otolaryngology of University of Minnesota in USA. Histopathologic observation of temporal bones showed bilateral small glomus tympanicum tumors limited to the promontory. Although there was bilateral tinnitus, there was no pulsatile tinnitus, no conductive hearing loss and both of the tympanic membranes were intact. Histopathologic observation of temporal bones after death showed bilateral glomus tympanicum tumors. To our knowledge, this is the first reported case of bilateral glomus tympanicum tumors.

Structural Analysis of Tensor Tympani Muscle, Tympanic Diaphragm, Epitympanum, and Protympanum in Menière's Disease: a Human Temporal Bone Study.

HYPOTHESIS: We hypothesized that there would be significant anatomic differences of the tensor tympani muscle (TTM), tympanic diaphragm, epitympanum, and protympanum in patients with versus without Menière's disease. BACKGROUND: The effects of tenotomy on Menière's disease suggested it relieves the pressure on the inner ear of the contraction of the TTM and of negative middle ear pressure. METHODS: Using human temporal bones from patients with Menière's disease, two studies were conducted. We examined the presence of otitis media, cholesteatoma, and endolymphatic hydrops, the length, diameter, configuration, the volume of the TTM and tendon, and the area of the tympanic isthmus (Study 1). We examined the presence of otitis media, cholesteatoma and endolymphatic hydrops, and the area and volume of the protympanum (Study 2). RESULTS: In study 1, we observed no significant differences between the two groups. In study 2, we did not observe a small and narrow protympanum in the Menière's disease group. None of the ears in the Menière's or control groups had otitis media or cholesteatoma in either study. We observed hydrops in all the temporal bones of the Menière's disease group and none in the control groups. CONCLUSION: The position, configuration, and size of the tensor tympani muscle and tendon do not seem to play a role in the pathogenesis of Menière's disease. Because the tympanic isthmus and protympanum in Menière's disease are not smaller than controls and that none of the temporal bones had otitis media or cholesteatoma, it is unlikely that there was dysventilation in the middle ear.

Histopathology of tympanic membranes from patients with ventilation tubes.

OBJECTIVE: To evaluate the histopathologic changes in tympanic membranes (TMs) with ventilation tubes (VTs). METHODS: In this retrospective human temporal bone study our overall study group included 4 subgroups of TMs from deceased donors as follows: 24 with a history of VT insertion for chronic otitis media with effusion (COME-VT); 5 with a history of VT insertion for Meniere's disease (MD-VT); 33 without a history of VT insertion for chronic otitis media with effusion (COME); and 14 without a history of VT insertion for Meniere's disease (MD). We classified the extent of migration of the outer keratinized squamous epithelium onto the inner surface of TM perforations and noted the presence and location of tympanosclerosis, of atrophy, of perforation, and/or of cholesteatoma formation. RESULTS: Tympanosclerosis occurred in 14/24 TMs in the COME-VT subgroup; 2/5, MD-VT; 7/33, COME; and 0/14, MD. The VT insertion site was mostly in the anteroinferior (63%) quadrant of the TM; tympanosclerosis occurred more frequently in the posteroinferior (42%) and posterosuperior (33%) quadrants. We found no significant correlation between the location of tympanosclerosis and the VT insertion site (P>0.05). Atrophy occurred in 7/24 TMs in the COME-VT subgroup; 3/5, MD-VT; 8/33, COME; and 2/14, MD. We found no significant correlation between the location of atrophy and the VT insertion site; however, atrophy was located mostly in the anteroinferior quadrant (one of the most common VT insertion sites) of the TM. Regarding the ingrowth of keratinized epithelium, the mucocutanous junction was detected at any point at the inner surface of the TM in 50% of the specimens. We observed intratympanic cholesteatoma formation in 2/24 TMs in the COME-VT subgroup. CONCLUSION: TM changes due to VT insertion are more common than previously realized. Meticulous otomicroscopic evaluation of the TM is necessary during tympanomastoidectomies in order to prevent the intratympanic inclusion pearls and squamous epithelial ingrowth to prevent any further cholesteatoma formation.

Evidence against the mucosal traction theory in cholesteatoma.

OBJECTIVES: To investigate the distribution of ciliated epithelium in the human middle ear and its potential role in the formation of cholesteatoma. STUDY DESIGN: Comparative human temporal bone study. METHODS: We selected temporal bones from 14 donors with a diagnosis of cholesteatoma, 15 with chronic otitis media without retraction pockets, 14 with chronic otitis media with retraction pockets, 14 with cystic fibrosis (CF), and 16 controls. We mapped the distribution of the ciliated cells in the mucosal lining of the middle ear and tympanic membrane using three-dimensional reconstruction analysis, and counted the number of ciliated cells in the middle ear mucosa. RESULTS: Ciliated cells are extremely sparse in the epithelial lining of the lateral surface of the ossicles in the epitympanum and the medial surface of the tympanic membrane. Furthermore, there is a significant decrease in the number of ciliated cells in these areas in temporal bones with cholesteatoma, chronic otitis media, chronic otitis media with retraction pockets, and CF compared to controls. Ciliated cells most commonly are located at the hypotympanum and the Eustachian tube opening but not the tympanic membrane or epitympanum. CONCLUSION: The paucity of ciliated epithelial cells on the medial side of the tympanic membrane and the lateral surface of the ossicles in the epitympanum in cases with cholesteatoma and/or chronic otitis media do not support the mucosal migration theory of cholesteatoma formation. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1663-1667, 2018.

Neutrophil Extracellular Traps and Fibrin in Otitis Media: Analysis of Human and Chinchilla Temporal Bones.

Background: Bacterial resistance in acute otitis can result in bacterial persistence and biofilm formation, triggering chronic and recurrent infections. Objective: To investigate the middle ear inflammatory response to bacterial infection in human and chinchilla temporal bones. Design, Setting, and Participants: Six chinchillas underwent intrabullar inoculations with 0.5 mL of 106 colony-forming units (CFUs) of Streptococcus pneumoniae, serotype 2. Two days later, we counted bacteria in middle ear effusions postmortem. One ear from each chinchilla was processed in paraffin and sectioned at 5 µm. The opposite ear was embedded in epoxy resin, sectioned at a thickness of 1 µm, and stained with toluidine blue. In addition, we examined human temporal bones from 2 deceased donors with clinical histories of otitis media (1 with acute onset otitis media, 1 with recurrent infection). Temporal bones had been previously removed at autopsy, processed, embedded in celloidin, and cut at a thickness of 20 µm. Sections of temporal bones from both chinchillas and humans were stained with hematoxylin-eosin and immunolabeled with antifibrin and antihistone H4 antibodies. Main Outcome Measures: Histopatological and imminohistochemical changes owing to otitis media. Results: Bacterial counts in chinchilla middle ear effusions 2 days after inoculation were approximately 2 logs above initial inoculum counts. Both human and chinchilla middle ear effusions contained bacteria embedded in a fibrous matrix. Some fibers in the matrix showed positive staining with antifibrin antibody, others with antihistone H4 antibody. Conclusions and Relevance: In acute and recurrent otitis media, fibrin and neutrophil extracellular traps (NETs) are part of the host inflammatory response to bacterial infection. In the early stages of otitis media the host defense system uses fibrin to entrap bacteria, and NETs function to eliminate bacteria. In chronic otitis media, fibrin and NETs appear to persist.

Progression of changes in the sensorial elements of the cochlear and peripheral vestibular systems: The otitis media continuum.

Our study aimed to evaluate pathologic changes in the cochlear (inner and outer hair cells and stria vascularis) and vestibular (vestibular hair cells, dark, and transitional cells) sensorial elements in temporal bones from donors who had otitis media. We studied 40 temporal bones from such donors, which were categorized in serous otitis media (SOM), serous-purulent otitis media (SPOM), mucoid/mucoid-purulent otitis media (MOM/MPOM), and chronic otitis media (COM); control group comprised 10 nondiseased temporal bones. We found significant loss of inner and outer cochlear hair cells in the basal turn of the SPOM, MOM/MPOM and COM groups; significant loss of vestibular hair cells was observed in the MOM/MPOM and COM groups. All otitis media groups had smaller mean area of the stria vascularis in the basal turn of the cochlea when compared to controls. In conclusion, our study demonstrated more severe pathologic changes in the later stages of the continuum of otitis media (MOM/MPOM and COM). Those changes seem to progress from the basal turn of the cochlea (stria vascularis, then inner and outer hair cells) to the middle turn of the cochlea and to the saccule and utricle in the MOM/MPOM and COM stages.

A three-dimensional analysis of the endolymph drainage system in Ménière disease.

OBJECTIVES/HYPOTHESIS: To measure the volume of the endolymph drainage system in temporal bone specimens with Ménière disease, as compared with specimens with endolymphatic hydrops without vestibular symptoms and with nondiseased specimens STUDY DESIGN: Comparative human temporal bone analysis. METHODS: We generated three-dimensional models of the vestibular aqueduct, endolymphatic sinus and duct, and intratemporal portion of the endolymphatic sac and calculated the volume of those structures. We also measured the internal and external aperture of the vestibular aqueduct, as well as the opening (if present) of the utriculoendolymphatic (Bast's) valve and compared the measurements in our three study groups. RESULTS: The volume of the vestibular aqueduct and of the endolymphatic sinus, duct, and intratemporal endolymphatic sac was significantly lower in the Ménière disease group than in the endolymphatic hydrops group (P <.05). The external aperture of the vestibular aqueduct was also smaller in the Ménière disease group. Bast's valve was open only in some specimens in the Ménière disease group. CONCLUSIONS: In temporal bones with Ménière disease, the volume of the vestibular aqueduct, endolymphatic duct, and intratemporal endolymphatic sac was lower, and the external aperture of the vestibular aqueduct was smaller as compared with bones from donors who had endolymphatic hydrops without vestibular symptoms and with nondiseased bones. The open status of the Bast's valve in the Ménière disease group could be secondary to higher retrograde endolymph pressures caused by smaller drainage systems. These anatomic findings could correlate with the reason that some patients with hydrops develop clinical symptoms, whereas others do not. LEVEL OF EVIDENCE: N/A Laryngoscope, 127:E170-E175, 2017.

Deterioration of Vestibular Cells in Labyrinthitis.

OBJECTIVE: To quantitatively assess the effect of serous labyrinthitis, suppurative labyrinthitis, and labyrinthitis ossificans on vestibular hair cells, dark cells, and transitional cells. METHODS: We examined human temporal bone specimens with serous labyrinthitis, suppurative labyrinthitis, and labyrinthitis ossificans, then compared them with age-matched control groups without labyrinthitis. We evaluated the density of type I and II vestibular hair cells, dark cells, and transitional cells in the peripheral sensorial organs. RESULTS: The mean density of type I vestibular hair cells in the maculae of the saccule significantly differed between the serous labyrinthitis group and its control group. The loss of type I and II vestibular hair cells in all of the peripheral sensorial organs was significantly higher in the suppurative labyrinthitis group than in its control group. The mean density of dark cells in the lateral and posterior semicircular canals was significantly lower in the suppurative labyrinthitis group than in its control group. The mean density of type I and II vestibular hair cells, dark cells, and transitional cells was significantly lower in the labyrinthitis ossificans group than in its control group. CONCLUSION: The loss of vestibular hair cells and degenerative changes in dark cells and transitional cells could affect vestibular function in patients with labyrinthitis.

A 3-D analysis of the protympanum in human temporal bones with chronic ear disease.

Eustachian tube dysfunction is believed to be an important factor to cholesteatoma development and recurrence of disease after surgical treatment. Although many studies have described prognostic factors, evaluation methods, or surgical techniques for Eustachian tube dysfunction, they relied on the soft tissues of its structure; little is known about its bony structure-the protympanum-which connects the Eustachian tube to the tympanic cavity, and can also be affected by several inflammatory conditions, both from the middle ear or from the nasopharynx. We studied temporal bones from patients with cholesteatoma, chronic otitis media (with and without retraction pockets), purulent otitis media, and non-diseased ears, looking for differences between the volume of the protympanum, the diameter of the Eustachian tube isthmus, and the distance between the anterior tympanic annulus and the promontory. Light microscopy and 3-D reconstruction software were used for the measurements. We observed a decrease of volume in the lumen of the four middle ear diseased ears compared to the control group. We observed a significant decrease in the volume of the protympanic space in the cholesteatoma group compared to the chronic otitis media group. We also observed a decrease in the bony space (protympanum space) in cholesteatoma, chronic otitis media with retraction pockets, and purulent otitis media compared to the control group. We found a correlation in middle ear diseases and a decrease in the middle ear space. Our findings may suggest that a smaller bony volume in the protympanic area may trigger middle ear dysventilation problems.

Pathologic Changes of the Peripheral Vestibular System Secondary to Chronic Otitis Media.

OBJECTIVE: To evaluate the histopathologic changes of dark, transitional, and hair cells of the vestibular system in human temporal bones from patients with chronic otitis media. STUDY DESIGN: Comparative human temporal bone study. SETTING: Otopathology laboratory. SUBJECTS AND METHODS: To compare the density of vestibular dark, transitional, and hair cells in temporal bones with and without chronic otitis media, we used differential interference contrast microscopy. RESULTS: In the chronic otitis media group (as compared with the age-matched control group), the density of type I and type II hair cells was significantly decreased in the lateral semicircular canal, saccule, and utricle (P < .05). The density of type I cells was also significantly decreased in the chronic otitis media group in the posterior semicircular canal (P = .005), but that of type II cells was not (P = .168). The mean number of dark cells was significantly decreased in the chronic otitis media group in the lateral semicircular canal (P = .014) and in the posterior semicircular canal (P = .002). We observed no statistically significant difference in the density of transitional cells between the 2 groups (P > .1). CONCLUSION: The findings of our study suggest that the decrease in the number of vestibular sensory cells and dark cells could be the cause of the clinical symptoms of imbalance of some patients with chronic otitis media.

Cochlear changes in serous labyrinthitis associated with silent otitis media: A human temporal bone study.

PURPOSE: To determine histopathological findings in the cochlea of human temporal bones with serous labyrinthitis. MATERIALS AND METHODS: We compared human temporal bones with serous labyrinthitis (20 cases) associated with silent otitis media and without serous labyrinthitis (20 cases) to study location of serous labyrinthitis, the degree of endolymphatic hydrops, number of spiral ganglion cells and hair cells, loss of fibrocytes in the spiral ligament, and areas of the spiral ligament and stria vascularis. RESULTS: The serous labyrinthitis caused significant loss of outer hair cells in the lower basal (P=0.006), upper basal (P=0.005), and lower middle (P=0.011) cochlear turns, and significant increase in the degree of endolymphatic hydrops than the control group (P=0.036). No significant difference was found in the loss of inner hair cells, in the number of spiral ganglion cells and fibrocytes in the spiral ligament, and in areas of the stria vascularis and spiral ligament (P>0.05). CONCLUSIONS: Serous labyrinthitis resulted in significant loss of outer hair cells and significant increase in the degree of endolymphatic hydrops.

Histopathologic Evaluation of Vascular Findings in the Cochlea in Patients With Presbycusis.

IMPORTANCE: Age-related changes in cochlear vessel wall thickness in human temporal bones have not been described previously. OBJECTIVES: To compare thickness of the spiral modiolar artery and strial capillaries and to investigate strial atrophy and vessel loss in temporal bones with and without presbycusis. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case-control study examined the autopsy reports of 1024 patients in the temporal bone collection at the University of Minnesota. Inclusion criteria consisted of being 60 years or older with sensorineural hearing loss and progression of hearing loss with age (presbycusis group). Age-matched controls had no record of hearing loss. All patients underwent pure-tone audiometry. Exclusion criteria included a history of otologic disease, ototoxic drug use, head or acoustic trauma, or systemic disease. Data were collected from October 1, 2013, to October 1, 2014. MAIN OUTCOMES AND MEASURES: Vessel wall thickness in the modiolar artery and strial vessels, the strial area, and number of strial vessels were measured under light microscopy. RESULTS: Among the 1024 autopsy reports examined, 11 patients (19 temporal bones) with presbycusis (7 men and 4 women; age range, 67-88 years; mean [SD] age, 78 [7] years]) and 15 controls (24 temporal bones) (7 men and 8 women; age range, 67-94 years; mean [SD] age, 79 [8] years) met the inclusion criteria. Compared with the control group, the presbycusis group had significantly increased mean (SD) thickness of vessel walls in the modiolar arteries (6.73 [2.39] vs 5.55 [0.86] µm; P = .02) and the strial capillaries in the lower basal (1.57 [0.21] vs 1.39 [0.15] µm; P = .005), upper basal (1.62 [0.28] vs 1.40 [0.13] µm; P < .001), lower middle (1.68 [0.22] vs 1.39 [0.20] µm; P < .001), upper middle (1.74 [0.39] vs 1.40 [0.19] µm; P = .01), and apical (1.70 [0.36] vs 1.47 [0.21] µm; P = .04) turns of the cochlea. Compared with the control group, the presbycusis group had significant loss of strial area in the lower basal (6614 [1559] vs 8790 [1893] µm2; P = .002), upper basal (6387 [2211] vs 9105 [2700] µm2; P < .001), lower middle (5140 [1471] vs 7269 [2181] µm2; P = .003), upper middle, (5583 [1742] vs 7206 [2258] µm2; P = .02), and apical (4286 [1604] vs 6535 [2454] µm2; P < .001) turns of the cochlea; in the vessel area in the lower basal turn (74.65 [127.74] vs 124.92 [89.04] µm2; P = .01); and in the number of vessels in the lower basal (1.00 [0.78] vs 1.94 [0.93]; P = .008) and lower middle (1.00 [0.78] vs 1.94 [0.93]; P = .04) turns of the cochlea. CONCLUSIONS AND RELEVANCE: The histopathologic findings of increased thickness of the vascular walls of the modiolar arteries and stria vascularis, increased strial atrophy, and decreased number of strial vessels may have led to decreased cochlear microcirculation. Deficiency in the circulation and perfusion of the cochlea may be a factor in presbycusis.

Effects of Intralabyrinthine Hemorrhage on the Cochlear Elements: A Human Temporal Bone Study.

HYPOTHESIS: To compare histopathologic findings in the cochlea of human temporal bones with versus without intralabyrinthine hemorrhage. BACKGROUND: Hemorrhagic labyrinthitis can cause sensorineural damage, sudden hearing loss, and vertigo. Yet, to our knowledge, no studies have quantitatively described histopathologic effects of intralabyrinthine hemorrhage on the elements of the cochlea. METHODS: We analyzed 46 human temporal bone samples from 23 patients with unilateral intralabyrinthine hemorrhage (23 samples from ears with intralabyrinthine hemorrhage and 23 samples from contralateral ears without). We noted the location of hemorrhage in the inner ear, the degree of endolymphatic hydrops, the number of spiral ganglion cells and hair cells, mean loss of fibrocytes in spiral ligament, and areas of the stria vascularis and spiral ligament. RESULTS: Intralabyrinthine hemorrhage caused significant loss of outer hair cells in the lower basal (p = 0.001), upper basal (p = 0.005), and lower middle (p = 0.012) cochlear turns. The degree of endolymphatic hydrops was significantly different between the hemorrhagic and contralateral sides (p = 0.011). But we found no significant difference between the 2 sides in the number of inner hair cells, spiral ganglion cells, and fibrocytes, or in the areas of the stria vascularis and spiral ligament between the two groups (p > 0.05). CONCLUSION: These findings suggest that such patients could be good candidates for hearing aid or cochlear implant if they have profound sensorineural hearing loss.

Quantitative Vestibular Labyrinthine Otopathology in Temporal Bones with Vestibular Schwannoma.

OBJECTIVE: Dizziness associated with vestibular schwannoma is usually ascribed to retrolabyrinthine mechanisms. The goal of this study was to determine if quantitative peripheral vestibular (labyrinthine) otopathology was present in a series of patients with vestibular schwannoma. STUDY DESIGN: Comparative human temporal bone study. SETTING: Otopathology laboratory. SUBJECTS AND METHODS: Temporal bones from 12 subjects with unilateral sporadic vestibular schwannoma were included. Based on differential interference contrast microscopy, type I and II vestibular hair cell counts were performed on each vestibular sense organ with minimal autolysis in which the neuroepithelium was oriented perpendicular to the plane of section. Hair cell densities (cells per 0.01-mm(2) surface area) and the presence of endolymphatic hydrops and precipitate within the endolymph or perilymph were compared between the tumor ears and the contralateral (control) ears. RESULTS: Compared with the contralateral ears, vestibular schwannoma ears had significantly more endolymphatic hydrops (P = .049) and precipitate in the endolymph and perilymph (P = .005), lower densities of type I and II vestibular hair cells in the lateral canal cristae (mean differences, respectively: 25.2 [P = .001] and 10.8 [P < .001]) and utricle (mean differences, respectively: 26.8 and 10.4 [P < .001]), and lower densities of type I hair cells and the same density of type II hair cells in the saccule (mean differences, respectively: 26.5 [P < .001] and 0.9 [P = .46]). CONCLUSION: Peripheral vestibular otopathology, manifested as reductions of vestibular hair cell densities, was identified in ears with vestibular schwannoma. Labyrinthine as well as retrolabyrinthine pathology may contribute to tumor-related vestibular dysfunction.

Quantitative assessment of vestibular otopathology in otosclerosis: A temporal bone study.

OBJECTIVES/HYPOTHESIS: To determine if peripheral vestibular otopathology is present in human temporal bones with otosclerosis. STUDY DESIGN: Comparative human temporal bone study. METHODS: Seventy-four human temporal bones from 46 subjects with otosclerosis (mean age of 61 ± 18 years) and 20 within histologically normal limits from 17 subjects (mean age of 59 ± 14 years) were included in this study. Temporal bones with otosclerosis were divided into those with and without endosteal involvement. Using differential interference contrast microscopy at 1008× magnification, type I and type II vestibular hair cell counts were performed on each vestibular sense organ in which the neuroepithelia was oriented perpendicular to the plane of section. The organ-specific cell densities (cells/0.01 mm(2) surface area) were compared between the groups with and without endosteal involvement, and also compared to counts in the nonotosclerosis control group using Student's t-test. RESULTS: Mean type I and type II hair cell densities of all vestibular structures in the group with endosteal involvement were significantly lower compared to the group without endosteal involvement. Mean type I and type II hair cell densities of all vestibular structures in the group with endosteal involvement were also significantly lower compared to the control group, but they were not in the group without endosteal involvement compared to the control group. CONCLUSION: Endosteal involvement of otosclerotic foci is associated with vestibular hair cell loss that may contribute to the vestibular symptoms in otosclerosis. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:E118-E122, 2016.

Volume of the epitympanum and blockage of the tympanic isthmus in chronic otitis media: a human temporal bone study.

HYPOTHESIS: To compare the differences in the epitympanic bony volume and the area of the tympanic isthmus (TI) in human temporal bones (HTBs) with chronic otitis media (COM) having epitympanic involvement and those without COM. BACKGROUND: TI is crucial for mastoid and epitympanic ventilation. Previous studies demonstrated that the area of TI was related to the degree of HTBs pneumatization and that COM caused suppressed pneumatization of the middle ear, decreasing volume. To our knowledge, there have been no studies, however, investigating the correlation between COM and epitympanic volume or between the TI and the epitympanic volume. METHODS: Eleven HTBs from children with COM and 11 HTBs without COM (control group) were examined. Three-dimensional models were generated from HTB histopathologic slides with reconstruction software (AMIRA), and epitympanic bony volumes were measured and compared between the two groups.The narrowest aerated/bony TI area was also measured and compared to investigate the correlation between the bony epitympanic volume and the TI area within each group. RESULTS: There were no significant differences in epitympanic bony volume or bony TI area between the groups. Aerated TI area in the COM group was significantly smaller than that in the control group (p < 0.01). There was no relationship between aerated TI area and bony epitympanic volume in the two groups. In the COM group, there was a negative correlation between bony TI area and epitympanic volume (p < 0.001). CONCLUSION: This study suggests that congenital or developmental stenosis of the TI may not be associated with epitympanic pathology, but blockage of TI with soft tissue pathology may be associated with chronic tissue pathology in COM.

Pneumococcal PspA and PspC proteins: potential vaccine candidates for experimental otitis media.

OBJECTIVE: Otitis media is the most commonly diagnosed disease in ambulatory care and Streptococcuspneumoniae continues to be the most common bacterial agent. Bacterial resistance to antibiotics underscores the need for better vaccines. Current pneumococcal conjugate vaccines are modestly protective against otitis media; however, limited serotype coverage and serotype replacement have led to the investigation of pneumococcal proteins as potential vaccine candidates. Two proteins, pneumococcal surface proteins A (PspA) and C (PspC) are important virulence factors, expressed by virtually all strains. Although a number of pneumococcal proteins have been investigated in other infection sites, these proteins can have diverse organ-specific effects. In this study, we investigated the viability and virulence of single (PspA(-) and PspC(-)) and double (PspA(-)/PspC(-)) mutants of pneumococcal PspA and PspC proteins in the chinchilla middle ear. METHODS: Bullae of 24 chinchillas were inoculated with 0.5 ml of 10(6) colony forming units (CFUs)/ml bacteria: 6 with wild-type D39 strain; 6 with PspA(-); 6 with PspC(-); and 6 with PspA(-)/PspC(-) isogenic mutant strains. Bacterial CFU levels in middle ear effusions and light microscopic analysis of the number of inflammatory cells in the round window membrane (RWM) were compared 48 h after inoculation. RESULTS: At 48 h, CFUs in middle ears were increased for wild-type and PspC(-) strains compared to inoculum levels; however, they were significantly less for the group inoculated with the PspC(-) strain compared to wild-type strain. No bacteria were detected in the PspA(-) and PspA(-)/PspC(-) groups. The number of inflammatory cells in the RWM was significantly higher in wild-type compared to the PspA(-), PspC(-), and PspA(-)/PspC(-) groups. No significant difference in number of inflammatory cells was observed between any pairs of groups inoculated with mutant strains. CONCLUSION: Viability and virulence of the PspC(-) strain were similar to the wild-type strain. The single PspA(-) and double PspA(-)/PspC(-) mutants were highly attenuated in the ear. Bacterial clearance of the PspA(-)/PspC(-) double mutant was indistinguishable from that of the PspA mutant. These studies provide no reason to exclude PspC from a multi-component protein vaccine containing PspA.