Publications by authors named "Patricia Schachern"

85 Publications

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

Biomolecules 2021 Jan 29;11(2). Epub 2021 Jan 29.

Immusoft Corp, Minneapolis, MN 55413, USA.

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.
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http://dx.doi.org/10.3390/biom11020189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911293PMC
January 2021

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

Eur Arch Otorhinolaryngol 2021 Feb 1;278(2):331-338. Epub 2020 Jun 1.

Department of Otolaryngology Head and Neck Surgery, University of Minnesota, Minneapolis, MN, USA.

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.
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http://dx.doi.org/10.1007/s00405-020-06094-5DOI Listing
February 2021

Bilateral glomus tympanicum tumors: Human temporalbone study.

Clin Pract 2018 Jul 12;8(3):1035. Epub 2018 Jul 12.

Department of Otolaryngology, University of Minnesota, Minneapolis, MN, USA.

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.
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http://dx.doi.org/10.4081/cp.2018.1035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151334PMC
July 2018

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

Otol Neurotol 2018 04;39(4):499-505

Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota.

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.
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http://dx.doi.org/10.1097/MAO.0000000000001748DOI Listing
April 2018

Evidence against the mucosal traction theory in cholesteatoma.

Laryngoscope 2018 07 8;128(7):1663-1667. Epub 2017 Oct 8.

Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota.

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.
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http://dx.doi.org/10.1002/lary.26940DOI Listing
July 2018

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

JAMA Otolaryngol Head Neck Surg 2017 10;143(10):990-995

Department of Otolaryngology University of Minnesota, Minneapolis.

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.
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http://dx.doi.org/10.1001/jamaoto.2017.1320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710261PMC
October 2017

Histopathology of tympanic membranes from patients with ventilation tubes.

Auris Nasus Larynx 2018 Jun 31;45(3):427-432. Epub 2017 Jul 31.

Department of Otolaryngology, University of Minnesota, Minneapolis, MN, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.anl.2017.07.017DOI Listing
June 2018

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

Hear Res 2017 08 26;351:2-10. Epub 2017 May 26.

Department of Otorhinolaryngology Head and Neck Surgery, Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina, Rua dos Otonis, 700 - Piso Superior - Vila Clementino, São Paulo, SP 04025 002, Brazil.

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.
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http://dx.doi.org/10.1016/j.heares.2017.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557455PMC
August 2017

Deterioration of Vestibular Cells in Labyrinthitis.

Ann Otol Rhinol Laryngol 2017 Feb 24;126(2):89-95. Epub 2016 Nov 24.

1 Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, USA.

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.
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http://dx.doi.org/10.1177/0003489416675356DOI Listing
February 2017

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

Eur Arch Otorhinolaryngol 2017 Mar 22;274(3):1357-1364. Epub 2016 Nov 22.

Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, 2001 6th Street SE, Lions Research Building Room 210, Minneapolis, MN, 55455, USA.

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.
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http://dx.doi.org/10.1007/s00405-016-4396-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022743PMC
March 2017

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

Laryngoscope 2017 05 21;127(5):E170-E175. Epub 2016 Jul 21.

Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota, U.S.A.

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.
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http://dx.doi.org/10.1002/lary.26155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253118PMC
May 2017

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

Otolaryngol Head Neck Surg 2016 09 10;155(3):494-500. Epub 2016 May 10.

Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota, USA

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.
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http://dx.doi.org/10.1177/0194599816646359DOI Listing
September 2016

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

Am J Otolaryngol 2016 Mar-Apr;37(2):83-8. Epub 2015 Oct 8.

Department of Otolaryngology, University of Minnesota, Minneapolis, MN, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.amjoto.2015.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785270PMC
December 2016

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

JAMA Otolaryngol Head Neck Surg 2016 Feb;142(2):173-8

Department of Otolaryngology, University of Minnesota, Minneapolis.

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.
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http://dx.doi.org/10.1001/jamaoto.2015.3163DOI Listing
February 2016

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

Otol Neurotol 2016 Feb;37(2):132-6

*Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, U.S.A. †Gebze Fatih State Hospital, Otolaryngology Division, Gebze, Kocaeli, Turkey ‡Giresun A. Ilhan Ozdemir State Hospital, Otolaryngology Division, Giresun, Turkey §Paparella Ear Head and Neck Institute, Minneapolis, Minnesota, U.S.A.

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.
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http://dx.doi.org/10.1097/MAO.0000000000000927DOI Listing
February 2016

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

Laryngoscope 2016 Mar 26;126(3):E118-22. Epub 2015 Aug 26.

Department of Otolaryngology-Head and Neck Surgery, University of Minnesota.

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.
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http://dx.doi.org/10.1002/lary.25523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755806PMC
March 2016

Quantitative Vestibular Labyrinthine Otopathology in Temporal Bones with Vestibular Schwannoma.

Otolaryngol Head Neck Surg 2016 Jan 25;154(1):150-6. Epub 2015 Aug 25.

Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota, USA

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.
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http://dx.doi.org/10.1177/0194599815601070DOI Listing
January 2016

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

Otol Neurotol 2015 Feb;36(2):254-9

*Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, U.S.A.; †Department of Otolaryngology, Tokyo Medical University, Tokyo, Japan; and ‡Paparella Ear Head and Neck Institute, Minneapolis, Minnesota, U.S.A.

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.
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http://dx.doi.org/10.1097/MAO.0000000000000623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297250PMC
February 2015

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

Int J Pediatr Otorhinolaryngol 2014 Sep 24;78(9):1517-21. Epub 2014 Jun 24.

Departments of Otolaryngology, University of Minnesota, Minneapolis, MN, United States.

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.
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http://dx.doi.org/10.1016/j.ijporl.2014.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129636PMC
September 2014

Differences in the diameter of facial nerve and facial canal in bell's palsy--a 3-dimensional temporal bone study.

Otol Neurotol 2014 Mar;35(3):514-8

*University of Minnesota, Minneapolis, Minnesota, U.S.A.; and †Santa Casa of Sao Paulo School of Medicine, Sao Paulo, Brazil.

Unlabelled: Bell's palsy is hypothesized to result from virally mediated neural edema. Ischemia occurs as the nerve swells in its bony canal, blocking neural blood supply. Because viral infection is relatively common and Bell's palsy relatively uncommon, it is reasonable to hypothesize that there are anatomic differences in facial canal (FC) that predispose the development of paralysis. Measurements of facial nerve (FN) and FC as it follows its tortuous course through the temporal bone are difficult without a 3D view. In this study, 3D reconstruction was used to compare temporal bones of patients with and without history of Bell's palsy.

Methods: Twenty-two temporal bones (HTBs) were included in the study, 12 HTBs from patients with history of Bell's palsy and 10 healthy controls. Three-dimensional models were generated from HTB histopathologic slides with reconstruction software (Amira), diameters of the FC and FN were measured at the midpoint of each segment.

Results: The mean diameter of the FC and FN was significantly smaller in the tympanic and mastoid segments (p = 0.01) in the BP group than in the controls. The FN to FC diameter ratio (FN/FC) was significantly bigger in the mastoid segment of BP group, when compared with the controls. When comparing the BP and control groups, the narrowest part of FC was the labyrinthine segment in control group and the tympanic segment in the BP.

Conclusion: This study suggests an anatomic difference in the diameter of FC in the tympanic and mastoid segments but not in the labyrinthine segment in patients with Bell's palsy.
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http://dx.doi.org/10.1097/MAO.0000000000000240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158913PMC
March 2014

The pathology of silent otitis media: a predecessor to tympanogenic meningitis in infants.

Int J Pediatr Otorhinolaryngol 2014 Mar 18;78(3):451-4. Epub 2013 Dec 18.

Department of Otolaryngology, University of Minnesota, Minneapolis, MN, USA. Electronic address:

Objective: To determine the association of bacteria embedded within a fibrous matrix in the middle and inner ear in infants with tympanogenic meningitis.

Methods: Thirty-one cases with meningitis from the human temporal bone collection at the University of Minnesota were screened to select those with tympanogenic meningitis. Inclusion criteria for tympanogenic meningitis were acute meningitis with histopathological evidence of chronic otitis media, and no other source of infection. The presence of labyrinthitis and pathologic changes such as granulation tissue, fibrosis, cholesterol granuloma, cholesteatoma, tympanic membrane perforation, tympanosclerosis, and the type of effusion were noted. The extent and location of bacteria embedded in a fibrous matrix were also explored.

Results: Seventeen temporal bones, from nine cases that included two females and seven males, ranging in age from five to twenty-three months, met our criteria of tympanogenic meningitis. Eighty two percent of these temporal bones had bacteria within the fibrous matrices (BFM). BFM were located in one anatomical region in one temporal bone and multiple anatomic regions in sixteen temporal bones. The most common locations were the areas near the oval and round windows. They were also commonly seen in the epitympanum, facial recess, and supratubal recess. BFM within the inner ear were observed in the scala tympani and modiolus in the middle and basal turns of the cochleae of nine temporal bones. In one of these temporal bones, BFM were seen in the internal auditory canal. Labyrinthitis was seen in all ears. The tympanic membrane was intact in all cases. BFM were not seen in three temporal bones from two patients. In one case only one side was available for study.

Conclusions: Our findings show an association between the presence of BFM in the ear with chronic pathologic changes and tympanogenic meningitis. Potential pathways of bacteria from the middle ear include hematogeous spread and/or direct spread to dura through the tympanic tegmen, and/or to the inner ear through the oval and round windows, and from there to the modiolus and the meninges. Chronic pathologic changes in the middle ear behind an intact tympanic membrane and the lack of ear symptoms may result in potentially serious sequelae and complications in infant age groups. There should be a heightened awareness of this condition.
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http://dx.doi.org/10.1016/j.ijporl.2013.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935507PMC
March 2014

Viability and virulence of pneumolysin, pneumococcal surface protein A, and pneumolysin/pneumococcal surface protein A mutants in the ear.

JAMA Otolaryngol Head Neck Surg 2013 Sep;139(9):937-43

Department of Otolaryngology, University of Minnesota, Minneapolis.

Importance: Understanding how pneumococcal proteins affect the pathology of the middle ear and inner ear is important for the development of new approaches to prevent otitis media and its complications.

Objectives: To determine the viability and virulence of Streptococcus pneumoniae mutants deficient in pneumolysin (Ply-) and pneumococcal surface protein A (PspA-) in the chinchilla middle ear.

Design: Bullae of chinchillas were inoculated bilaterally with wild-type (Wt), Ply-, PspA-, and Ply-/PspA- strains. Bacterial colony-forming units (CFUs) in middle ear effusions were counted at 48 hours. The CFUs of the PspA- group were also counted at 6 to 36 hours after inoculation. Temporal bone histopathological results were compared.

Setting And Participants: Twenty-seven chinchillas in an academic research laboratory.

Exposure: Chinchilla middle ears were inoculated with S pneumoniae to produce sufficient volumes of effusions and noticeable histopathological changes in the ears.

Main Outcomes And Measures: The CFU counts in the middle ear effusions and histopathological changes were compared to determine the effect of pneumococcal protein mutations on chinchilla ears.

Results: At 48 hours, CFUs in middle ears were increased for the Wt and Ply-/PspA- strains, but Ply- remained near inoculum level. No bacteria were detected in the PspA- group. The CFUs of PspA- decreased over time to a low level at 30 to 36 hours. In vitro, PspA- in Todd-Hewitt broth showed an increase in bacterial growth of 2 logs at 43 hours, indicating PspA- susceptibility to host defenses in vivo. The PspA- and Ply- groups had fewer pathologic findings than the Wt or Ply-/PspA- groups. Histopathological analysis showed significant differences in the number of bacteria in the scala tympani in the Wt group compared with the Ply-, PspA-, and Ply-/PspA- groups. The PspA- strain was the least virulent.

Conclusions And Relevance: The PspA- mutant was much less viable and less virulent in the ear than the Wt, Ply-, and Ply-/PspA- strains. There was no significant attenuation in the viability and virulence of the Ply-/PspA- mutant compared with the Wt or single mutants. The viability and virulence of pneumococcal mutants seemed to be protein and organ specific.
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http://dx.doi.org/10.1001/jamaoto.2013.4104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037925PMC
September 2013

Inner ear changes in mucopolysaccharidosis type I/Hurler syndrome.

Otol Neurotol 2012 Oct;33(8):1323-7

Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Objective: Mucopolysaccharidosis type I/Hurler syndrome is an autosomal recessive disease caused by a deficiency of α-L-iduronidase activity. Recurrent middle ear infections and hearing loss are common complications in Hurler syndrome. Although sensorineural and conductive components occur, the mechanism of sensorineural hearing loss has not been determined. The purpose of this study is to evaluate the quantitative inner ear histopathology of the temporal bones of patients with Hurler syndrome.

Patients: Eleven temporal bones from 6 patients with Hurler syndrome were examined. Age-matched healthy control samples consisted of 14 temporal bones from 7 cases.

Main Outcome Measures: Temporal bones were serially sectioned in the horizontal plane and stained with hematoxylin and eosin. The number of spiral ganglion cells, loss of cochlear hair cells, area of stria vascularis, and cell density of spiral ligament were evaluated using light microscopy.

Results: There was no significant difference between Hurler syndrome and healthy controls in the number of spiral ganglion cells, area of stria vascularis, or cell density of spiral ligament. The number of cochlear hair cells in Hurler syndrome was significantly decreased compared with healthy controls.

Conclusion: Auditory pathophysiology in the central nerve system in Hurler syndrome remains unknown; however, decreased cochlear hair cells may be one of the important factors for the sensorineural component of hearing loss.
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http://dx.doi.org/10.1097/MAO.0b013e3182659cc3DOI Listing
October 2012

Peripheral vestibular system in Down syndrome: quantitative assessment of vestibular histopathology.

Otolaryngol Head Neck Surg 2011 Feb;144(2):280-3

Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Objective: To evaluate the maturity of the peripheral vestibular system in Down syndrome by examining the number of Scarpa's ganglion cells and the density of vestibular hair cells.

Study Design: Case-control study using human temporal bones.

Setting: Tertiary academic center, otopathology laboratory.

Subjects And Methods: Sixteen temporal bones from 8 patients with Down syndrome and 15 control temporal bones from 8 individuals with no history of otologic disease were selected. Hypoplasia of the lateral semicircular canal (LSC) and vestibule was investigated by measuring the dimensions of the structures. Scarpa's ganglion cells were counted under light microscopy. The vestibular hair cells were counted in the LSC crista and the utricular and saccular maculae under differential interference contrast (Nomarski) microscopy and expressed as density.

Results: The patients with Down syndrome were divided into 2 groups: with and without LSC hypoplasia. The number of Scarpa's ganglion cells and the density of vestibular hair cells were significantly smaller in both groups of patients with Down syndrome than in the control group. There was no significant difference in the number of Scarpa's ganglion cells or the density of vestibular hair cells between the groups with and without LSC hypoplasia.

Conclusion: The peripheral vestibular system, including Scarpa's ganglion cells and vestibular hair cells, is hypoplastic irrespective of the vestibular malformation in Down syndrome.
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http://dx.doi.org/10.1177/0194599810391204DOI Listing
February 2011

Effect of apolactoferrin on experimental pneumococcal otitis media.

Arch Otolaryngol Head Neck Surg 2010 Nov;136(11):1127-31

Department of Otolaryngology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.

Objective: To find the effect of apolactoferrin administration on the middle and inner ears after experimentally induced pneumococcal otitis media.

Design: Histopathologic and morphometric analysis of the middle and inner ears.

Setting: University of Minnesota, Minneapolis.

Subjects: Ten chinchillas.

Interventions: The middle ear cavities of chinchillas were inoculated bilaterally with type 2 wild-type Streptococcus pneumoniae. Twenty-four hours later, the ears of 5 of the animals were injected with phosphate-buffered saline (PBS) and the other 5 with human apolactoferrin. The animals were killed 24 hours after the last injection. Bacterial counts were made of the middle ear effusions, and the cochleae were processed for histologic analysis. The thickness of the round window membranes and bacterial and inflammatory cell infiltration of the round window membranes, and scala tympani and damage of the hair cells and stria vascularis were compared for these 2 groups of animals.

Main Outcome Measures: Comparison of inflammatory and bacterial cells in the middle and inner ears, and damage to inner ear structures.

Results: Bacterial plate counts of middle ear effusions (P  = .005) and the number of inflammatory cells in the round window membrane (P  = .047) were significantly lower in the apolactoferrin group compared with the group treated with PBS.

Conclusion: Further investigation of apolactoferrin as a nonantibiotic approach for the treatment of otitis media and its complications is needed to confirm its safety and efficacy.
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http://dx.doi.org/10.1001/archoto.2010.192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022344PMC
November 2010

Marrow-middle ear connections: a potential cause of otogenic meningitis.

Otol Neurotol 2011 Jan;32(1):77-80

Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, USA.

Hypothesis: We hypothesize that the connections between the hematopoietic bone marrow and middle ear is a potential cause of childhood otogenic meningitis.

Background: Although it is known that there is a causal relationship between otitis media and bacterial meningitis, the relationship has never been satisfactorily established. Human fetal and infant temporal bones prepared for light microscopic evaluation revealed direct connections between the hematopoietic bone marrow and middle ear. We noted this difference in anatomy between the infant middle ear and the adult middle ear.

Methods: We studied 10 temporal bones from 5 infants in each group: meningitis group with otitis media who died of meningitis, control Group 1 without otitis media, and control Group 2 with otitis media who died of diseases other than meningitis. A quantitative analysis of the frequency of connections between the hematopoietic bone marrow and middle ear was performed. The correlation between unabsorbed mesenchyme and otitis media also was investigated.

Results: The frequency of connections was significantly higher in order of the meningitis group, control Group 2, and control Group 1. The degree of unabsorbed mesenchyme tended to be more severe in order of the meningitis group, control Group 2, and control Group 1.

Conclusion: The prevalence of connections between the hematopoietic bone marrow and middle ear in patients with meningitis and otitis media is high. A higher prevalence of connections in infants with otitis media could increase the risk for otogenic meningitis in them.
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http://dx.doi.org/10.1097/MAO.0b013e3181f6c866DOI Listing
January 2011

Posterior semicircular canal dehiscence: a histopathologic human temporal bone study.

Otol Neurotol 2010 Sep;31(7):1122-7

Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota 55455, U.S.A.

Background: Posterior semicircular canal dehiscence has been shown to cause ear symptoms.

Objective: To evaluate the incidence of dehiscence of the posterior semicircular canal, thin bone overlying the posterior semicircular canal, and the normal development of the distance between the posterior semicircular canal and posterior cranial fossa.

Methods: The shortest distance between the posterior semicircular canal and posterior cranial fossa was measured in 1,051 adult human temporal bones (557 cases), and temporal bones with a distance less than 0.1 mm were evaluated. The shortest distance also was measured in 4 fetal temporal bones (2 cases) and 110 temporal bones from children.

Results: Of the 1,051 temporal bones, 23 temporal bones (2.2%) had a distance less than 0.1 mm between the posterior semicircular canal and posterior cranial fossa. Two temporal bones (0.2%) had posterior semicircular canal dehiscence, and 2 temporal bones had microfractures in the thin bone; however, related clinical symptoms were not confirmed. In children, the distance between the posterior semicircular canal and the posterior cranial fossa increased with age (rho = 0.68, p < 0.01).

Conclusion: The histopathologic incidence of posterior semicircular canal dehiscence was lower than the previous radiographic reports. The dehiscence of the posterior semicircular canal may be due to a developmental anomaly. In our study, none of the cases with a distance less than 0.1 mm had apparent symptoms related to canal dehiscence syndrome. Other factors, in addition to thinning of the bone, may be required to cause the clinical manifestations.
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http://dx.doi.org/10.1097/MAO.0b013e3181eb3309DOI Listing
September 2010

Histopathological morphometric study of cochleosaccular dysplasia in Dalmatian dogs.

Int J Pediatr Otorhinolaryngol 2010 Aug 12;74(8):934-8. Epub 2010 Jun 12.

Brasilia University Medical School - Capes, Fulbright Scholarship, Brasilia, Brazil.

Objective: To analyze temporal bones of deaf Dalmatian dogs from 5 days after birth to adulthood to better understand the pathogenesis of cochleosaccular dysplasia.

Methods: This is an experimental animal histopathological temporal bone study that included two groups of temporal bones. Group I consisted of 41 temporal bones from deaf Dalmatian dogs and group II of 25 temporal bones from 15 "normal" aged-matched, hearing Black Labradors. Morphometric analysis included: stria vascularis and spiral ligament area measurements, and cell counts of spiral ganglion, Scarpa's ganglion, and hair cells of saccular macula.

Results: The following findings were significantly less in deaf Dalmatian group compared to hearing Labradors: (1) cellular area of the stria vascularis in all cochlear turns; (2) cellular area of spiral ligament in the inferior part of the basal turn; (3) cellular density of spiral ganglion cells within segments III and IV; (4) number of Scarpa's ganglion cells; and (5) density of saccular hair cells types I and II. A borderline negative correlation was found between average density of spiral ganglion cells of segments III and IV and age in group I. Young deaf animals showed some cochlear hair cells, however in adult dogs all hair cells were replaced by supporting cells.

Conclusion: General pattern of cochleosaccular dysplasia is variable, even when only one etiology, the genetic one, is involved. The gradual degeneration of inner ear elements in the cochleosaccular degeneration might indicate that early intervention might be crucial to stop the progression of cochleosaccular dysplasia.
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http://dx.doi.org/10.1016/j.ijporl.2010.05.020DOI Listing
August 2010

Cochlear changes in presbycusis with tinnitus.

Am J Otolaryngol 2011 May-Jun;32(3):215-20. Epub 2010 Apr 30.

Department of Otolaryngology, University of Minnesota, Minneapolis, MN55455, USA.

Objectives: The pathophysiology of tinnitus is obscure and its treatment is therefore elusive. Significant progress in this field can only be achieved by determining the mechanisms of tinnitus generation, and thus, histopathologic findings of the cochlea in presbycusis with tinnitus become crucial. We revealed the histopathologic findings of the cochlea in subjects with presbycusis and tinnitus.

Material And Methods: The subjects were divided into 2 groups, presbycusis with tinnitus (tinnitus) group and presbycusis without tinnitus (control) group, with each group comprising 8 temporal bones from 8 subjects. We quantitatively analyzed the number of spiral ganglion cells, loss of cochlear inner and outer hair cells, and areas of the stria vascularis and spiral ligament.

Results: There was a significantly greater loss of outer hair cells in the tinnitus group compared with the control group in the basal and upper middle turns. The stria vascularis was more atrophic in the tinnitus group compared with the control group in the basal turn.

Conclusions: Tinnitus is more common in patients with presbycusis who have more severe degeneration of outer hair cells and stria vascularis.
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http://dx.doi.org/10.1016/j.amjoto.2010.02.001DOI Listing
August 2011

Pathologic correlations of otologic symptoms in acute lymphocytic leukemia.

Am J Otolaryngol 2011 Jan-Feb;32(1):13-8. Epub 2009 Dec 22.

Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, USA.

Objectives: To assess the clinicopathologic correlations of otologic complaints in patients with acute lymphocytic leukemia.

Design: Otologic complaints and histologic findings were evaluated in 25 temporal bones of 13 acute lymphocytic leukemia patients.

Results: Nine patients had a history of otologic complaints, including hearing loss, otalgia, otorrhea, and vertigo in 5, 3, 3, and 2 patients, respectively. Hemorrhage was most commonly observed in the middle ear (6 patients, 9 temporal bones) and was also observed in cochlea (4 patients, 4 temporal bones), and vestibule (6 patients, 6 temporal bones). Leukemic infiltration was observed in the petrous apex (13 patients, 24 temporal bones), middle ear (7 patients, 14 temporal bones), cochlea (3 patients, 4 temporal bones), vestibule (3 patients, 4 temporal bones), and internal auditory canal (5 patients, 8 temporal bones). Inflammatory changes were observed in the cochlea (5 patients, 8 temporal bones) and vestibule (5 patients, 8 temporal bones). Middle ear effusion containing floating tumor cells was observed in 4 temporal bones of 3 patients. Irreversible histopathologic changes of the middle ear, such as the destruction of the ossicles, perforation of the tympanic membrane, and granulation tissues were observed in 5 temporal bones of 4 patients.

Conclusions: Ear involvement is common in acute lymphocytic leukemia patients. With prolonged survival due to the progress of treatment, the diagnosis and treatment of nonhematopoietic system symptoms, such as ear problems due to acute lymphocytic leukemia, have become more important.
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http://dx.doi.org/10.1016/j.amjoto.2009.08.006DOI Listing
April 2011