Publications by authors named "Sebahattin Cureoglu"

135 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

Cochlear turns measurements in patients with meningitis: A histopathological study.

Laryngoscope Investig Otolaryngol 2020 Jun 6;5(3):506-510. Epub 2020 May 6.

Department of Ophthalmology, Otolaryngology and Head and Neck Surgery Ribeirão Preto Faculty of Medicine (FMRP-USP) Ribeirão Preto São Paulo Brazil.

Objective: To demonstrate the cochlear turns area changes among patients with a history of meningitis, through otopatologic study.

Methods: We performed an analysis of the area of the bony cochlear turns and the cochlear lumen of the horizontal sections containing the modiolus and the area of the basal turn at the level of round window, in temporal bones obtained from patients with a history of meningitis and compared to a nondiseased control group.

Results: The mean area of the bony walls and the lumen of all cochlear turns are reduced within the meningitis group. Patients who presented a time from the diagnosis of meningitis to death longer than 30 days had a significant reduction in the cochlear turns area, as compared to the control group.

Conclusion: Future studies may further correlate audiologic outcomes, cochlear volume, and cochlear area among patients with meningitis.
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http://dx.doi.org/10.1002/lio2.383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314461PMC
June 2020

A Structural Analysis of Tympanic Compartments of the Middle Ear in Patients With Down's Syndrome: A Temporal Bone Study.

Otol Neurotol 2020 09;41(8):1149-1157

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

: Hypothesis: There may be findings peculiar to the temporal bones of children with Down's syndrome (DS). The purpose of this study is to investigate the temporal bone histopathology of the children with DS.

Background: Otitis media with effusion is a highly prevalent condition with DS. Knowledge of the volume of the tympanic compartments and the area of the tympanic isthmus might be important to find out the pathogenesis of highly prevalent otitis media with effusion in those patients.

Methods: We compared the volume of the epitympanum, mesotympanum, and the areas of the tympanic isthmus and tympanic orifice of eustachian tube in temporal bones from patients with DS. We also investigated the eustachian tube histopathologically.

Results: The mean volume of the epitympanum and the mesotympanum was significantly smaller in the DS group than the control group. We found no significant difference in the mean diameter of the protympanic opening and tympanic orifice between the two groups. The mean narrowest area of the aerated and bony tympanic isthmus also was not significantly different between the two groups. An immature development of eustachian tube and cartilage was seen. We found mesenchyme remaining at the epitympanum and/or mesotympanum in all specimens in the DS group, and in five specimens in the control group.

Conclusion: In the presence of the small middle ear, poorly developed eustachian tube, and tensor muscle, a vicious circle occurs, making otitis media with effusion difficult to resolve.
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http://dx.doi.org/10.1097/MAO.0000000000002715DOI Listing
September 2020

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

Cytomegalovirus-induced pathology in human temporal bones with congenital and acquired infection.

Am J Otolaryngol 2019 Nov - Dec;40(6):102270. Epub 2019 Aug 2.

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

Objective: Publications on histopathology of human temporal bones with cytomegalovirus (CMV) infection are limited. We aim to determine histopathology of the inner ears and the middle ears in human temporal bones with congenital and acquired CMV infections.

Methods: Temporal bones from 2 infants with congenital and 2 adults with acquired CMV infection were evaluated by light microscopy.

Results: Two infants with congenital CMV infection showed striking pathological changes in the inner ear. There was a hypervascularization of the stria vascularis in the cochlea of the first infant, but no obvious loss of outer and inner hair cells was seen in the organ of Corti. However, cytomegalic cells and a loss of outer hair cells were found in the cochlea of the second infant. The vestibular organs of both infants showed cytomegalic cells, mostly located on dark cells. There was a loss of type I and type II hair cells in the macula of the saccule and utricle. Loss of hair cells and degeneration of nerve fibers was also seen in the semicircular canals. Both infants with congenital infection showed abundant inflammatory cells and fibrous structures in the middle ear cavity. No evidence of cytomegalic cells and hair cell loss was found in the cochlea or vestibular labyrinth in acquired CMV infection.

Conclusions: In two infants with congenital CMV infection, the cochlea, vestibule, and middle ear were highly affected. Temporal bones of adult donors with acquired viral infection showed histological findings similar to donors of the same age without ear disease.
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http://dx.doi.org/10.1016/j.amjoto.2019.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858532PMC
April 2020

Histopathology of Inner Ear Malformations: Potential Pitfalls for Cochlear Implantation.

Otol Neurotol 2019 09;40(8):e839-e846

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

Hypothesis: The presence of bony inner ear malformations may associate with a number of anatomical abnormalities affecting the middle ear structures. Those malformations may create pitfalls and complications for cochlear implantation.

Background: Inner ear malformations associate with varying degrees of hearing loss, and frequently require cochlear implantation for hearing rehabilitation. Therefore, the abnormalities affecting the middle- and inner-ear structures may increase the risk of surgical complications.

Methods: We examined 38 human temporal bones from donors with bony inner ear malformations. Using light microscopy, we analyzed the presence of abnormalities in the structures of the middle- and inner-ear.

Results: Our collection comprises of 38 specimens with inner-ear malformations (cochlear aplasia, n = 3; cochlear hypoplasia, n = 30; incomplete partition, n = 3; isolated vestibular malformation, n = 2). The anatomy of the middle ear was abnormal in most temporal bones with cochlear aplasia, cochlear hypoplasia, and incomplete partition type I (40%-100%). Some of those abnormalities (hypoplastic or obliterated mastoid, 55.2%; aplastic or obliterated round window, 71.0%; aberrant course of the facial nerve, 36.8%) may hinder the access to the round window using the conventional facial recess approach for cochlear implantation. The cochlear nerve and associated bony structures (internal auditory canal and bony canal for cochlear nerve) were normal in 71.0% of all temporal bones with inner ear malformations.

Conclusion: Each different type of malformation may create specific surgical challenges to surgeons. Comprehensive preoperative imaging is fundamental toward the surgical success of cochlear implants in patients with malformations. Alternatives to circumvent those middle- and inner-ear abnormalities and potential complications are further discussed.
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http://dx.doi.org/10.1097/MAO.0000000000002356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377297PMC
September 2019

Quantitative Assessment of Inner Ear Histopathologic Findings in Partial Trisomy of 13.

Otol Neurotol 2019 09;40(8):e854-e857

Department of Otolaryngology Head & Neck Surgery, University of Minnesota.

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http://dx.doi.org/10.1097/MAO.0000000000002347DOI Listing
September 2019

Cochleosaccular (Scheibe) dysplasia in dogs: A temporal bone study.

Can J Vet Res 2019 Jan;83(1):11-16

Department of Internal Medicine (Keskin, Albasan) and Department of Surgery (Sancak), Faculty of Veterinary Medicine, University of Ankara, Ankara, Turkey; Department of Otolaryngology, Head and Neck Surgery, School of Medicine, University of Minnesota, Lions Research Building, Room 210, Mayo Mail Code 2873, 2001 6th Street SE, Minneapolis, Minnesota 55455, USA (Keskin, Albasan, Sancak, Cureoglu); Paparella Ear Head & Neck Institute, Minneapolis, Minnesota, USA (Paparella); Department of Otolaryngology, Massachusetts Eye and Ear Infirmary (Mini-fellowship), Harvard University, Boston, Massachusetts, USA (Keskin).

The objective of this study was to evaluate any otopathologic changes in temporal bone specimens from dogs with deafness related to cochleosaccular (Scheibe) dysplasia (CSD). We used the canine temporal bone collections of the Otopathology Laboratory at the University of Minnesota and of the Massachusetts Eye and Ear Infirmary at Harvard University in Boston. Our morphometric analysis included measuring the areas of the stria vascularis and the spiral ligament and counting the number of spiral ganglion cells. In addition, we noted the presence of the organ of Corti and cochlear hair cells, assessed the location of Reissner's membrane and the saccular membrane, and counted the number of both Type I and Type II vestibular hair cells in the macule of the saccule and vestibular ganglion cells. In the group of specimens from dogs with cochleosaccular dysplasia, we observed generalized degeneration in the cochlea and a significantly decreased number of Type I and Type II vestibular hair cells and vestibular ganglion cells. As hereditary deafness is presently untreatable with known therapeutic methods, dogs with cochleosaccular dysplasia should not be considered for breeding. Future therapeutic approaches, such as stem cell therapies, should be designed to target all the elements of the cochlea in addition to the saccule as it was found that both are affected in dogs with CSD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318820PMC
January 2019

Quantitative assessment of vestibular otopathology in granulomatosis with polyangitis: A temporal bone study.

Laryngoscope Investig Otolaryngol 2018 Dec 5;3(6):473-477. Epub 2018 Nov 5.

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

Objective: To investigate the temporal bone histopathology of vasculitis, especially in the vestibular organs, in granulomatosis with polyangitis (GPA).

Methods: Using light and differential interference contrast microscopy, we examined 12 human temporal bones from six deceased GPA patients and 12 histopathologically normal human temporal bones from six deceased age-matched patients.

Results: In the GPA group, three patients had undergone tympanostomy tube placement. Two of them had suffered mixed hearing loss; one, sensorineural hearing loss; and one, conductive hearing loss. Of the 12 specimens in the GPA group, the granulation tissue invaded the round window niche in seven; cochlear hair cells were not preserved in five. Hemosiderin was deposited in the stria vascularis in eight specimens, in the ampulla or semicircular duct in 10, and in the vestibule in three. The spiral ligament showed severe loss of cellularity in two specimens. In the GPA group, type I vestibular hair cell density was significantly decreased; however, type II vestibular hair cell density did not significantly differ between the GPA group and the control group.

Conclusion: Our histopathologic findings in human temporal bone specimens of GPA patients delineated changes in the tympanic membrane, middle ear cavity, round window membrane, organ of Corti, stria vascularis, spiral ligament, ampulla, semicircular duct, and vestibule. Type I vestibular hair cell density significantly decreased in the GPA group, as compared with the control group.

Level Of Evidence: N/A.
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http://dx.doi.org/10.1002/lio2.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302790PMC
December 2018

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

Otopathology in the United States: History, Current Situation, and Future Perspectives.

Otol Neurotol 2018 10;39(9):1210-1214

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

: Human temporal bone studies have documented the pathophysiologic basis of many pathologic conditions and diseases affecting the ear, contributing to the development of specific clinical knowledge and pathology-oriented treatments. Researchers dedicated to the study of anatomy and histology of the temporal bone emanated from Europe to the United States during the first part of the 20th Century. The first otopathology laboratory was founded in the United States in 1924, at Johns Hopkins University; over time, the otopathology laboratories-considered by some authors as "gold mines" for studying ear diseases-became numerous and very prolific. However, today, only three of the temporal bone laboratories are still running and producing scientific knowledge to the Otology/Neurotology field: the ones at Harvard Medical School, University of Minnesota, and University of California. Molecular biologic assay techniques and new microscopy and computer equipment broadened the possibilities for temporal bone studies; however, the current funding for those laboratories are insufficient to cover the costs for processing and studying human temporal bones. The main objective of this study is to briefly describe the history, current situation, and future perspectives of the otopathology laboratories in the United States.
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http://dx.doi.org/10.1097/MAO.0000000000001942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557446PMC
October 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

Histopathologic Changes of Human Vestibular Epithelia in Intralabyrinthine Hemorrhage.

Ann Otol Rhinol Laryngol 2017 Jun 24;126(6):445-450. Epub 2017 Mar 24.

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

Objective: To determine whether intralabyrinthine hemorrhage affects vestibular hair cells, dark cells, and transitional cells in human temporal bones.

Methods: We examined 9 temporal bone specimens from 9 deceased donors with unilateral intralabyrinthine hemorrhage (the hemorrhage group) along with their 9 contralateral temporal bone specimens without hemorrhage (the control group). We estimated the density of type I and type II hair cells in all peripheral sensorial organs (including the cristae of the superior, lateral, and posterior semicircular canals, as well as the maculae of the saccule and utricle). We also estimated the density of dark and transitional cells in the lateral and posterior semicircular canals.

Results: The loss of type I hair cells in the cristae of the superior, lateral, and posterior semicircular canals and in the maculae of the saccule and utricle was significantly higher in the hemorrhage group, as compared with the control group ( P < .05). The density of type II hair cells in the cristae of the superior and posterior canals and in the macula of the saccule significantly differed between the hemorrhage group and the control group ( P < .05).

Conclusion: The loss of vestibular hair cells might be the cause of vestibular symptoms in patients with intralabyrinthine hemorrhage.
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http://dx.doi.org/10.1177/0003489417700646DOI Listing
June 2017

Secondary Endolymphatic Hydrops.

Otol Neurotol 2017 06;38(5):774-779

*Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania †Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota ‡Department of Internal Medicine of Ankara University, Ankara, Turkey §Department of Otolaryngology, Otopathology Laboratory, University of Minnesota ||The Paparella Ear, Head, and Neck Institute, Minneapolis, Minnesota.

Hypothesis: A review of the most recent literature will provide clinicians with an update of secondary endolymphatic hydrops, aiding in diagnosis and treatment of affected patients.

Background: Secondary endolymphatic hydrops is a pathologic finding of the inner ear resulting in episodic vertigo and intermittent hearing loss. It is a finding for which extensive research is being performed.

Methods: A review of the most recent literature on secondary endolymphatic hydrops was performed using PubMed literature search.

Results: Recent investigation of secondary endolymphatic hydrops has brought attention to traumatic and inflammatory insults as causes for secondary endolymphatic hydrops. Such etiologies, including postsurgical effects of cochlear implantation and endolymphatic sac ablation; otosclerosis and its operative intervention(s); acoustic and mechanical trauma; medications; and systemic inflammatory processes, have been determined as causes of secondary lymphatic hydrops. Histopathological slides for many of the etiologies of secondary endolymphatic hydrops are presented.

Conclusion: Through an understanding of the pathophysiology and etiologies of secondary endolymphatic hydrops, clinicians will gain a better understanding of this complex disease process, which will aid in treatment of patients with this disease process.
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http://dx.doi.org/10.1097/MAO.0000000000001377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425947PMC
June 2017

Histopathology of Meniere's disease.

Oper Tech Otolayngol Head Neck Surg 2016 Dec;27(4):194-204

Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota, USA; Paparella Ear Head and Neck Institute, Minneapolis, Minnesota, USA.

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http://dx.doi.org/10.1016/j.otot.2016.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344024PMC
December 2016

Changes in the inner ear structures in cystic fibrosis patients.

Int J Pediatr Otorhinolaryngol 2017 Jan 16;92:108-114. Epub 2016 Nov 16.

Department of Otolaryngology, Head & Neck Surgery, University of Minnesota Minneapolis, MN, USA. Electronic address:

Objective: Although prolonged use of antibiotics is very common in cystic fibrosis (CF) patients, no studies have assessed the changes in both cochlear and peripheral vestibular systems in this population.

Methods: We used human temporal bones to analyze the density of vestibular dark, transitional, and hair cells in specimens from CF patients who were exposed to several types of antibiotics, as compared with specimens from an age-matched control group with no history of ear disease or antibiotic use. Additionally, we analyzed the changes in the elements of the cochlea (hair cells, spiral ganglion neurons, and the area of the stria vascularis). Data was gathered using differential interference contrast microscopy and light microscopy.

Results: In the CF group, 83% of patients were exposed to some ototoxic drugs, such as aminoglycosides. As compared with the control group, the density of both type I and type II vestibular hair cells was significantly lower in all structures analyzed; the number of dark cells was significantly lower in the lateral and posterior semicircular canals. We noted a trend toward a lower number of both inner and outer cochlear hair cells at all turns of the cochlea. The number of spiral ganglion neurons in Rosenthal's canal at the apical turn of the cochlea was significantly lower; furthermore, the area of the stria vascularis at the apical turn of the cochlea was significantly smaller.

Conclusions: Deterioration of cochlear and vestibular structures in CF patients might be related to their exposure to ototoxic antibiotics. Well-designed case-control studies are necessary to rule out the effect of CF itself.
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http://dx.doi.org/10.1016/j.ijporl.2016.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344023PMC
January 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

Does Otosclerosis Affect Dark and Transitional Cells in the Human Vestibular Labyrinth?

Otol Neurotol 2017 02;38(2):234-238

*Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, U.S.A. †Department of Otolaryngology-Head and Neck Surgery, Gebze Fatih State Hospital, Gebze, Kocaeli, Turkey ‡Paparella Ear Head & Neck Institute, Minneapolis, Minnesota, U.S.A.

Hypothesis: The density of vestibular dark cells (DCs) and vestibular transitional cells (TCs) can be quantitatively decreased in human temporal bones with otosclerosis.

Background: Previous reports have shown that otosclerosis can lead to vestibular symptoms.

Methods: We examined 61 human temporal bone specimens from 52 deceased donors with otosclerosis group-with and without endosteal involvement (EI), and with and without endolymphatic hydrops (EH)-versus 25 specimens from 18 age-matched controls. Using light microscopy, we evaluated the nonsensory epithelium of the lateral semicircular canal (LSC) and posterior semicircular canal (PSC) of the human vestibular labyrinth, focusing on the density of DCs and TCs.

Results: In both the LSC and the PSC, as compared with the control group, the mean density of DCs significantly decreased in the EI (+) group, in the EI (+) and EH (+) subgroup, and in the EI (+) and EH (-) subgroup (p < 0.05). In addition, we found a significant difference in the mean density of DCs between the EI (+) group and the EI (-) group in the LSC and in the PSC (p < 0.05). But we found no significant difference in the mean density of TCs in any of the otosclerosis groups or subgroups as compared with the control group (p > 0.05).

Conclusion: We found a decrease in the density of DCs associated with EI in human temporal bone specimens with otosclerosis, regardless of the presence of EH. This decrease might cause damage in ion and water transportation, leading to vestibular symptoms.
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http://dx.doi.org/10.1097/MAO.0000000000001272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222754PMC
February 2017

Epitympanum volume and tympanic isthmus area in temporal bones with retraction pockets.

Laryngoscope 2016 11 23;126(11):E369-E374. Epub 2016 Apr 23.

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

Objectives/hypothesis: To compare the volume of the epitympanic space, as well as the area of the tympanic isthmus, in human temporal bones with retraction pockets to those with chronic otitis media without retraction pockets and to those with neither condition.

Study Design: Comparative human temporal bone study.

Methods: We generated a three-dimensional model of the bony epitympanum and measured the epitympanic space. We also compared the area of the tympanic isthmus.

Results: The mean total volume of the epitympanum was 40.55 ± 7.14 mm in the retraction pocket group, 50.03 ± 8.49 mm in the chronic otitis media group, and 48.03 ± 9.16 mm in the neither condition group. The mean volume of the anterior, lateral, and medial compartments in temporal bones in the retraction pocket group was significantly smaller than in the two control groups (P < 0.05). Total epitympanic volume was also significantly smaller in the retraction pocket group than in both control groups (P < 0.05). The mean area of the tympanic isthmus was significantly smaller in the retraction pocket group (8.11 ± 2.44 mm ) than in the chronic otitis media group (9.82 ± 2.06 mm ) or the neither condition group (10.66 ± 1.78 mm ) (P < 0.05).

Conclusion: Our data indicate that temporal bones with retraction pockets have a smaller volume bony epitympanum and a smaller tympanic isthmus area as compared with temporal bones from both control groups. The smaller volume tympanic isthmus in the retraction pocket group may suggest that a blockage in the aeration pathways to the epitympanum could create dysventilation, resulting in negative pressure and ultimately in retraction pockets and cholesteatomas.

Level Of Evidence: NA Laryngoscope, 126:E369-E374, 2016.
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http://dx.doi.org/10.1002/lary.25937DOI Listing
November 2016

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 Findings of the Cochlea in Labyrinthitis Ossificans Associated with the Round Window Membrane.

Otolaryngol Head Neck Surg 2016 10 24;155(4):635-40. Epub 2016 May 24.

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

Objective: To quantitatively demonstrate and classify the histopathologic changes in the cochlea of the human temporal bones with labyrinthitis ossificans (LO).

Study Design: Comparative human temporal bone study.

Setting: Tertiary academic medical center.

Subjects And Methods: We compared 23 temporal bone specimens from 19 deceased donors with LO associated with the round window membrane (RWM) and 27 age-matched specimens from 20 deceased donors without any otologic diseases. We focused on the location of LO in the inner ear, the intensity of endolymphatic hydrops, the number of spiral ganglion cells and cochlear hair cells, and the areas of the stria vascularis and spiral ligament. In addition, we created a new pathologic grading system for temporal bone specimens from deceased donors with LO associated with the RWM.

Results: We most often observed LO in the scala tympani of the basal cochlear turn. In the LO group (as compared with the control group), the intensity of endolymphatic hydrops was significantly increased; the number of spiral ganglion cells was significantly decreased in all segments; the loss of outer and inner hair cells was significantly increased in all turns of the cochlea; the atrophy of the stria vascularis was significantly greater in all turns of the cochlea; and atrophy of the spiral ligament was significantly greater in the basal and middle cochlear turn.

Conclusion: LO was associated with significant cochlear damage (to the spiral ganglion cells, cochlear hair cells, stria vascularis, and spiral ligament) and with increased intensity of endolymphatic hydrops.
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http://dx.doi.org/10.1177/0194599816651245DOI Listing
October 2016

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

Peripheral vestibular pathology in Mondini dysplasia.

Laryngoscope 2017 01 14;127(1):206-209. Epub 2016 Apr 14.

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

Objectives/hypothesis: In this study, our objective was to histopathologically analyze the peripheral vestibular system in patients with Mondini dysplasia.

Study Design: Comparative human temporal bone study.

Methods: We assessed the sensory epithelium of the human vestibular system with a focus on the number of type I and type II hair cells, as well as the total number of hair cells. We compared those numbers in our Mondini dysplasia group versus our control group.

Results: The loss of type I and type II hair cells in the cristae of the superior, lateral, and posterior semicircular canals, as well as in the saccular and utricular macula, was significantly higher in our Mondini dysplasia group than in our control group. The total number of hair cells significantly decreased in the cristae of the superior, lateral, and posterior semicircular canals, as well as in the saccular and utricular macula, in our Mondini dysplasia group.

Conclusion: Loss of vestibular hair cells can lead to vestibular dysfunction in patients with Mondini dysplasia.

Level Of Evidence: NA Laryngoscope, 127:206-209, 2017.
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http://dx.doi.org/10.1002/lary.25995DOI Listing
January 2017

Otopathologic Findings of Pena-Shokeir Syndrome Type I.

Ann Otol Rhinol Laryngol 2016 Aug 11;125(8):677-81. Epub 2016 Apr 11.

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

Background: Pena-Shokeir syndrome type I is a rare genetic disorder that includes multiple congenital facial and joint anomalies as well as pulmonary hypoplasia. Affected infants are usually premature, and 30% of them are stillborn. So far, studies have reported low-set ears in such infants, with no middle or inner ear findings.

Method: Histopathological study of human temporal bones with Pena-Shokeir syndrome type I.

Results: Our case report describes an infant with severely decreased number of spiral ganglion cells and number of outer and inner hair cells of the cochlea, mild loss of vestibular hair cells, hypoplasia in the facial nerves, and ischemic degeneration of Schwann cells in the modiolus.

Conclusion: Pena-Shokeir syndrome type I is associated with a degenerative process in the labyrinth.
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http://dx.doi.org/10.1177/0003489416642789DOI Listing
August 2016

Cochlear Histopathologic Findings in Patients With Systemic Lupus Erythematosus: A Human Temporal Bone Study.

Otol Neurotol 2016 06;37(5):593-7

*Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, U.S.A. †Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan ‡Department of Otolaryngology, Gebze Fatih State Hospital, Gebze, Kocaeli, Turkey §Department of Otolaryngology, Giresun A. Ilhan Ozdemir State Hospital, Giresun, Turkey ||Department of Dermatology, University of Minnesota, Minneapolis, Minnesota, U.S.A. ¶Paparella Ear Head & Neck Institute, Minneapolis, Minnesota, U.S.A.

Hypothesis: We hypothesized that, in archived human temporal bone samples from patients with systemic lupus erythematosus (SLE), a pathologic condition exists in the stria vascularis and cochlear hair cells.

Background: Sensorineural hearing loss is a common feature in SLE patients. However, the pathophysiologic mechanism of cochlear dysfunction is unclear.

Methods: We examined 15 temporal bone samples from 8 SLE patients, along with 17 samples from 10 age-matched healthy control patients. The samples were serially sectioned in the horizontal plane and stained with hematoxylin and eosin. We determined the area of the stria vascularis in a midmodiolar section of each cochlear turn. Then, we made cytocochleograms and calculated the percentage of missing inner and outer hair cells.

Results: The area of the stria vascularis in our SLE group was significantly smaller than in our control group. The number of remaining inner hair cells in our SLE group was smaller than in our control group; however, the difference did not reach statistical significance. The loss of outer hair cells in our SLE group was significantly higher than in our control group. There was a tendency toward a positive correlation between the loss of cochlear hair cells and the duration of SLE.

Conclusion: The stria vascularis and cochlear hair cells are affected in SLE patients. Our findings could provide the histopathologic basis for the cochlear dysfunction, including sensorineural hearing loss, experienced by SLE patients.
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http://dx.doi.org/10.1097/MAO.0000000000001017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864109PMC
June 2016