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Biomedical subjects

Joseph B Nadol

Publications and source records attributed to Joseph B Nadol.

At least 19 recordsLinked to original sources
PubMed2006

Cochlin immunostaining of inner ear pathologic deposits and proteomic analysis in DFNA9 deafness and vestibular dysfunction.

Seven missense mutations and one in-frame deletion mutation have been reported in the coagulation factor C homology (COCH) gene, causing the adult-onset, progressive sensorineural hearing loss and vestibular disorder at the DFNA9 locus. Prevalence of COCH mutations worldwide is unknown, as there is no systematic screening effort for late-onset hearing disorders; however, to date, COCH mutations have been found on four continents and the possibility of COCH playing an important role in presbycusis and disorders of imbalance has been considered. Cochlin (encoded by COCH) has also been shown as a major target antigen for autoimmune sensorineural hearing loss. In this report, we present histopathology, immunohistochemistry and proteomic analyses of inner ear tissues from post-mortem DFNA9 temporal bone samples of an individual from a large Dutch kindred segregating the P51S mutation and adult human unaffected controls, and wild-type (+/+) and Coch null (-/-) knock-out mice. DFNA9 is an inner ear disorder with a unique histopathology showing loss of cellularity and aggregation of abundant homogeneous acellular eosinophilic deposits in the cochlear and vestibular labyrinths, similar to protein aggregation in well-known neurodegenerative disorders. By immunohistochemistry on the DFNA9 temporal bone sections, we have shown cochlin staining of the characteristic cochlear and vestibular deposits, indicating aggregation of cochlin in the same structures in which it is normally expressed. Proteomic analysis identified cochlin as the most abundant protein in mouse and human cochleae. The high-level expression and stability of cochlin in the inner ear, even in the absence and severe atrophy of the fibrocytes that normally express COCH, are shown through these studies and further elucidate the pathobiologic events occurring in DFNA9 leading to hearing loss and vestibular dysfunction.

Adult↗
PubMed2006

Revision mastoidectomy.

The first three priorities in surgery for chronic otitis media are (1) the elimination of progressive disease to produce a safe and dry ear, (2) modification of the anatomy of the tympanomastoid compartment to prevent recurrent disease, and (3) reconstruction of the hearing mechanism. The indications for revision following mastoidectomy for chronic otitis media thus involve failure to achieve any of these goals, including recurrent cholesteatoma, recurrent suppuration, recurrent perforation, or recurrent or residual conductive hearing loss. The focus of this article is the management of recurrent cholesteatoma or suppuration; that is, failure to achieve either of the first two priorities.

Cholesteatoma, Middle Ear↗
PubMed2006

Histopathology of the peripheral vestibular system after cochlear implantation in the human.

OBJECTIVES: The objective of this study was to describe the histology of the peripheral vestibular system in temporal bones from patients who in life had undergone cochlear implantation and to correlate the findings with previous reports of vestibular dysfunction after cochlear implantation. This is the first quantitative report of the impact of implantation on the vestibular neuronal end organ. METHODSThere were 19 temporal bones available for histologic study. Of these, 17 were suitable for the description of the morphology of the membranous labyrinth, 8 for counting Scarpa's ganglion cells, and 6 for measuring the densities of vestibular hair cells. The bones were fixed, cut, and stained according to previously published methods. Preferably, the implanted electrode was left in situ. Vestibular hair cells were counted with Nomarski's optics. RESULTS: Differences in Scarpa's ganglion cell counts and hair cell densities between the implanted and nonimplanted sides were not statistically significant. In 59% of the implanted bones, the cochlea was hydropic, and in the majority of these bones the saccule was collapsed. CONCLUSION: Cochlear implantation does not cause deafferentation of the peripheral vestibular system. Cochlear hydrops accompanied by saccular collapse is common and may cause attacks of vertigo of delayed onset, similar to Ménière's syndrome as previously reported in several clinical series. Hydrops could be caused by obstruction of endolymphatic flow in the ductus reuniens or in the hook portion of the cochlea or by damage to the lateral cochlear wall caused by implantation.

Aged↗
PubMed2006

Cochleosaccular dysplasia associated with a connexin 26 mutation in keratitis-ichthyosis-deafness syndrome.

OBJECTIVE: The objective of this study was to characterize the temporal bone phenotype associated with a mutation of GJB2 (encoding connexin 26). STUDY DESIGN: The authors conducted correlative clinical, molecular genetic, and postmortem histopathologic analysis. METHODS: The study subject was a male infant with keratitis-ichthyosis-deafness (KID) syndrome. We performed a nucleotide sequence analysis of GJB2 and a histopathologic analysis of the temporal bones. RESULTS: The subject was heterozygous for G45E, a previously reported KID syndrome mutation of GJB2. The primary inner ear abnormality was dysplasia of the cochlear and saccular neuroepithelium. CONCLUSIONS: GJB2 mutations can cause deafness in KID syndrome, and possibly in other GJB2 mutant phenotypes, by disrupting cochlear differentiation.

Cochlea↗
PubMed2006

Histopathology of the inner ear relevant to cochlear implantation.

The most common forms of severe hearing loss and deafness are related to morphological changes in the cochlea. Many individuals with such forms of hearing disorders have received cochlear implants. It has been assumed that preservation of spiral ganglion cells is important for success of cochlear implants. Preservation of ganglion cells is negatively correlated with the duration of the hearing loss. It has, however, not been possible to reveal a relationship between the degree of survival of spiral ganglion cells and performance of cochlear implants. It is important to understand the histopathological changes that follow cochlear implantation. Insertion of cochlear implants may cause trauma to the basilar membrane, the spiral lamina, and the spiral ligament. Rupture of the basilar membrane may occur. Over time, new bone forms at the cochleostomy and along the implant track. Further investigation is necessary to evaluate the causes of variability of behavioral measures of performance.

Adult↗
PubMed2006

Results after revision stapedectomy with malleus grip prosthesis.

Revision stapedectomy with a malleus grip prosthesis is a technically challenging otologic procedure. The prosthesis is usually longer and extends deeper into the vestibule than a conventional stapes prosthesis, creating the potential to affect the vestibular sense organs. The prosthesis also bypasses the ossicular joints, which are thought to play a role in protecting the inner ear from large changes in static pressure within the middle ear. The prosthesis is in close proximity to the tympanic membrane, thus increasing the risk for its extrusion. We reviewed our experience with revision stapedectomy with the Schuknecht Teflon-wire malleus grip prosthesis in 36 ears with a mean follow-up of 23 months. The air-bone gap was closed to within 10 dB in 16 ears (44%) and to within 20 dB in 26 ears (72%). The incidence of postoperative sensorineural hearing loss was 8% (3 ears). There were no dead ears. Extrusion of the prosthesis occurred in 1 case (3%). Nearly 50% of patients reported various degrees of vertigo or disequilibrium during the first 3 weeks after surgery. These vestibular symptoms resolved by 6 weeks in all but 1 case. We did not find evidence of damage to the inner ear due to the length of the prosthesis or due to the potential for direct transmission of changes in static pressures within the middle ear to the labyrinth. Our results are similar to those published in the literature for malleus attachment stapedectomy and conventional revision incus stapedectomy.

Adult↗
PubMed2006

The widely patent cochleovestibular communication of Edward Cock is a distinct inner ear malformation: implications for cochlear implantation.

OBJECTIVES: In 1838, Edward Cock described the anatomic findings in 4 inner ears with a widely patent communication between the cochlea and the vestibule that is now frequently referred to as the "common cavity deformity" and is often confused with Michel's "otocyst deformity." Little is known about the anatomic characteristics, including the presence of neural elements in this malformation. METHODS: Light microscopy and 2-dimensional and computerized 3-dimensional reconstructions were used to determine the histopathology and spiral ganglion cell counts in 7 temporal bones with a widely patent cochleovestibular communication. RESULTS: In all 7 specimens, the cochlea, vestibule, and semicircular canals were distinguishable and a bony defect resulting in an abnormal communication of perilymphatic space between the cochlea and vestibule was present. The ductus reuniens was abnormally wide in all. The cochlear duct varied from less than 1 turn to up to 2 turns. The mean spiral ganglion cells were estimated as a percentage of age-matched normal controls at 2.3%, 16.5%, and 26.8% when the cochlea was approximately 1, 1(1/2), and 2 turns, respectively (p = .007). The cribrose area consisted of a thin membrane in 2 specimens, and Rosenthal's canal openly communicated with the cerebrospinal fluid space in 3 specimens. The stapes footplate was abnormal in all 7 specimens and consisted of a central defect bridged by a thin membrane in 4 specimens. The facial nerve was dehiscent in 5 specimens (71%) and also followed an anomalous course in 2 specimens (28%). CONCLUSIONS: The widely patent cochleovestibular communication is a distinct inner ear malformation, recognition of which may have important clinical implications. Estimates of spiral ganglion cells can be predicted from the number of cochlear turns. Although cochlear implantation is feasible in patients with this malformation, a higher risk of cerebrospinal fluid gushers, facial nerve injuries, meningitis, and poor performance would be predicted. A better understanding of the anatomy will allow more effective surgical planning and techniques and may have a significant impact in improving outcomes.

Aged, 80 and over↗
PubMed2005

Histopathology of human cochlear implants: correlation of psychophysical and anatomical measures.

The cadavaric temporal bones of five subjects who underwent cochlear implantation during life (2 Nucleus and 3 Ineraid) were analyzed using two-dimensional (2D) reconstruction of serial sections to determine the number of surviving spiral ganglion cells (SGCs) in the region of each electrode of the implanted arrays. The last psychophysical threshold and maximum-comfortable sensation level measured for each electrode were compared to their respective SGC count to determine the across-electrode psychophysical variance accounted for by the SGC counts. Significant correlations between psychophysical measures and SGC counts were found in only two of the five subjects: one Nucleus implantee (e.g., r=-0.71; p<0.001 for threshold vs. count) and one Ineraid implantee (e.g., r=-0.86; p<0.05 for threshold vs. count). A three-dimensional (3D) model of the implanted cochlea was formulated using the temporal-bone anatomy of the Nucleus subject for whom the 2D analysis did not result in significant correlations between counts and psychophysical measures. Predictions of the threshold vs. electrode profile were closer to the measured profile for the 3D model than for the 2D analysis. These results lead us to hypothesize that 3D techniques will be required to asses the impact of peripheral anatomy on the benefit patients derive from cochlear implantation.

Cadaver↗
PubMed2005

Pathophysiology of Meniere's syndrome: are symptoms caused by endolymphatic hydrops?

BACKGROUND: The association of Meniere's syndrome with endolymphatic hydrops has led to the formation of a central hypothesis: many possible etiologic factors lead to hydrops, and hydrops in turn generates the symptoms. However, this hypothesis of hydrops as being the final common pathway has not been proven conclusively. SPECIFIC AIM: To examine human temporal bones with respect to the role of hydrops in causing symptoms in Meniere's syndrome. If the central hypothesis were true, every case of Meniere's syndrome should have hydrops and every case of hydrops should show the typical symptoms. METHODS: Review of archival temporal bone cases with a clinical diagnosis of Meniere's syndrome (28 cases) or a histopathologic diagnosis of hydrops (79 cases). RESULTS: All 28 cases with classical symptoms of Meniere's syndrome showed hydrops in at least one ear. However, the reverse was not true. There were 9 cases with idiopathic hydrops and 10 cases with secondary hydrops, but the patients did not exhibit the classic symptoms of Meniere's syndrome. A review of the literature revealed cases with asymptomatic hydrops (similar to the current study), as well as cases where symptoms of Meniere's syndrome existed during life but no hydrops was observed on histology. We also review recent experimental data where obstruction of the endolymphatic duct in guinea pigs resulted in cytochemical abnormalities within fibrocytes of the spiral ligament before development of hydrops. This result is consistent with the hypothesis that hydrops resulted from disordered fluid homeostasis caused by disruption of regulatory elements within the spiral ligament. CONCLUSION: Endolymphatic hydrops should be considered as a histologic marker for Meniere's syndrome rather than being directly responsible for its symptoms.

Adult↗
PubMed2005

Pathology and pathophysiology of idiopathic sudden sensorineural hearing loss.

BACKGROUND: The cause and pathogenesis of idiopathic sudden sensorineural hearing loss remain unknown. Proposed theories include vascular occlusion, membrane breaks, and viral cochleitis. AIMS: To describe the temporal bone histopathology in 17 ears (aged 45-94 yr) with idiopathic sudden sensorineural hearing loss in our temporal bone collection and to discuss the implications of the histopathologic findings with respect to the pathophysiology of idiopathic sudden sensorineural hearing loss. METHODS: Standard light microscopy using hematoxylin and eosin-stained sections was used to assess the otologic abnormalities. RESULTS: Hearing had recovered in two ears and no histologic correlates were found for the hearing loss in both ears. In the remaining 15 ears, the predominant abnormalities were as follows: 1) loss of hair cells and supporting cells of the organ of Corti (with or without atrophy of the tectorial membrane, stria vascularis, spiral limbus, and cochlear neurons) (13 ears); 2) loss of the tectorial membrane, supporting cells, and stria vascularis (1 ear); and 3) loss of cochlear neurons only (1 ear). Evidence of a possible vascular cause for the idiopathic sudden sensorineural hearing loss was observed in only one ear. No membrane breaks were observed in any ear. Only 1 of the 17 temporal bones was acquired acutely during idiopathic sudden sensorineural hearing loss, and this ear did not demonstrate any leukocytic invasion, hypervascularity, or hemorrhage within the labyrinth, as might be expected with a viral cochleitis. DISCUSSION: The temporal bone findings do not support the concept of membrane breaks, perilymphatic fistulae, or vascular occlusion as common causes for idiopathic sudden sensorineural hearing loss. The finding in our one case acquired acutely during idiopathic sudden sensorineural hearing loss as well as other clinical and experimental observations do not strongly support the theory of viral cochleitis. CONCLUSION: We put forth the hypothesis that idiopathic sudden sensorineural hearing loss may be the result of pathologic activation of cellular stress pathways involving nuclear factor-kappaB within the cochlea.

Adult↗
PubMed2005

Is word recognition correlated with the number of surviving spiral ganglion cells and electrode insertion depth in human subjects with cochlear implants?

OBJECTIVES/HYPOTHESIS: Speech perception scores using cochlear implants have ranged widely in all published series. The underlying determinants of success in word recognition are incompletely defined. Although it has been assumed that residual spiral ganglion cell population in the deaf ear may play a critical role, published data from temporal bone specimens from patients have not supported this hypothesis. The depth of insertion of a multichannel cochlear implant has also been suggested as a clinical variable that may be correlated with word recognition. In the current study these correlations were evaluated in 15 human subjects. STUDY DESIGN: Retrospective review of temporal bone histopathology. METHODS: Temporal bones were fixed and prepared for histological study by standard techniques. Specimens were then serially sectioned and reconstructed by two-dimensional methods. The spiral ganglion cells were counted, and the depth of insertion of the cochlear implant as measured from the round window was determined. Correlation analyses were then performed between the NU6 word scores and spiral ganglion cell counts and the depth of insertion. RESULTS: The segmental and total spiral ganglion cell counts were not significantly correlated (P > .50) with NU6 word scores for the 15 subjects. Statistically significant correlations were not achieved by separate analysis of implant types. Similarly, no significant correlation between the depth of insertion of the electrode array and postoperative NU6 word score was identified for the group. CONCLUSION: Although it is unlikely that the number of residual spiral ganglion cell counts is irrelevant to the determination of word recognition following cochlear implantation, there are, clearly, other clinical variables not yet identified that play an important role in determining success with cochlear implantation.

Aged↗
PubMed2005

Carcinoid tumor of the middle ear: clinical features, recurrences, and metastases.

OBJECTIVE: Present four new cases of carcinoid tumor of the middle ear, two of which developed late recurrences and regional metastases. Review the literature to identify the clinical features, rate of recurrence, and incidence of metastasis of carcinoid tumor of the middle ear. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral hospital. PATIENTS: Eligibility criteria consist of a diagnosis of carcinoid tumor of middle ear. INTERVENTION: Surgical excision of primary and metastatic disease. MAIN OUTCOME MEASURE: Clinical characteristics, rate of recurrence, and incidence of metastasis of carcinoid tumor of the middle ear. RESULTS: Forty-six patients with carcinoid tumor of the middle ear are included in this report, 42 patients were identified from a review of the literature, and 4 new patients are presented. The most common presenting symptom was hearing loss. Surgical excision was the treatment with radical mastoidectomy being the most common procedure. Ten (22%) patients developed locally recurrent disease, and four (9%) developed regional metastases. CONCLUSIONS: Carcinoid tumor of the middle ear is an infrequent cause of a middle ear mass, with only 46 cases published. Despite previous assertions of benignancy, the findings of this study suggest that carcinoid tumor of the middle ear is indeed a potential low-grade malignancy with documented metastatic potential. Almost all middle ear adenomatous tumors ("adenoma" and "carcinoid") show evidence of neuroendocrine differentiation, and so at least some middle ear carcinoids ("adenomas") appear to represent well-differentiated neuroendocrine carcinomas. Presentation and symptoms are consistent with a middle ear mass and rarely include carcinoid syndrome. Surgical treatment is recommended and tailored to the extent of disease. Patients with carcinoid tumor of the middle ear require indefinite follow-up for possible recurrence or metastasis.

Adolescent↗
PubMed2005

Effect of cochlear implantation on residual spiral ganglion cell count as determined by comparison with the contralateral nonimplanted inner ear in humans.

It is generally assumed that at least a minimal number of spiral ganglion cells is essential for successful speech perception with a cochlear implant. Although the insertion of a multichannel cochlear implant frequently results in loss of residual hearing in the implanted ear, this outcome does not imply that significant damage to residual populations of spiral ganglion cells has occurred. The purpose of the current study was to compare spiral ganglion cell counts in implanted and nonimplanted cochleas in 11 patients for whom both temporal bones were available and in whom a multichannel cochlear implant had been placed unilaterally. The temporal bones were processed for light microscopy by standard techniques. The cochleas were reconstructed by 2-dimensional methods. Spiral ganglion cell counts of the implanted and nonimplanted sides were compared by a paired t-test (2-tailed). The mean spiral ganglion cell counts for implanted and nonimplanted ears were not statistically different in the most basal three segments of the cochlea. However, the mean spiral ganglion cell count in segment 4 (apical segment) and the mean total spiral ganglion cell count were lower in the implanted cochleas than in the nonimplanted cochleas (p < .01). The results of this study suggest a modest decrease in the total spiral ganglion cell count in the implanted ears as compared to the nonimplanted ears, principally in the apical segment. Possible interpretations of this finding are discussed.

Aged↗
PubMed2004

Temporal bone histopathology in alport syndrome.

OBJECTIVE: To determine the histopathologic abnormalities within the cochlea in Alport syndrome. BACKGROUND: Alport syndrome, which manifests as hereditary nephritis and sensorineural hearing loss (SNHL), is caused by mutations in genes that code for the proportional, variant3, proportional, variant4, and proportional, variant5 chains of type IV collagen. The proportional, variant3, proportional, variant4, and proportional, variant5 chains of type IV collagen are present in the basement membrane of the organ of Corti. Previous temporal bone studies have failed to identify histopathologic correlates for the SNHL. METHODS: We examined temporal bones from nine individuals with a clinical diagnosis of Alport syndrome. One of our cases also had genetic testing that showed a mutation in the type IV collagen proportional, variant5 chain gene. RESULTS: By light microscopy, eight of nine cases demonstrated two unique pathologic changes: 1) a "zone of separation" between the basilar membrane and overlying cells of the organ of Corti and 2) presence of cells filling the tunnel of Corti and extracellular spaces of Nuel. The cytologic losses of hair cells, stria vascularis, and cochlear neuronal cells were insufficient to account for the observed SNHL in our cases. Electron microscopy was performed in four cases; all four demonstrated the following: 1) the zone of separation that was observed at light microscopy occurred between the basement membrane and the basilar membrane, 2) the cells within the tunnel of Corti and spaces of Nuel were morphologically similar to supporting cells, and 3) the basement membrane of strial capillaries and the spiral vessel (under the basilar membrane) were normal. CONCLUSIONS: The histopathologic correlates of cochlear involvement in Alport syndrome are abnormalities of the basement membrane of cells of the organ of Corti and dysmorphogenesis (cellular infilling of the tunnel and extracellular spaces) of the organ of Corti. We hypothesize that these abnormalities result in SNHL by altering cochlear micromechanics.

Adolescent↗
PubMed2004

Axial mesodermal dysplasia sequence: autopsy findings.

We describe an infant with the phenotype of the "axial mesodermal dysplasia spectrum" who had the oculo-auriculo-vertebral sequence and caudal dysgenesis. Postmortem studies identified anomalies of the middle ear ossicles, and muscles, in association with microtia and atresia of the external auditory canals, but no cerebral abnormalities.

Abnormalities, Multiple↗
PubMed2004

Histologic evaluation of the tissue seal and biologic response around cochlear implant electrodes in the human.

HYPOTHESIS: Histopathologic study of the tissue seal and biologic response around cochlear implant electrodes in patients who had received a cochlear implant during life could provide clues concerning the pathogenesis of meningitis after cochlear implantation. BACKGROUND: Bacterial meningitis has been reported as an infrequent complication of cochlear implantation using a variety of electrode designs. The cause of meningitis in cochlear implant recipients has not been firmly established. In an analogous surgical situation, namely stapedectomy, delayed meningitis could occur as a complication of ipsilateral acute suppurative otitis media in which there was open communication between the middle ear and perilymph. METHODS: Twenty-one temporal bones from 20 individuals who had undergone cochlear implantation during life were studied by light microscopy. All sections passing through the cochleostomy site and electrode track were examined to evaluate the tissue seal at the cochleostomy, the presence or absence of an extracochlear electrode sheath, and finally, to seek evidence of a cellular inflammatory response near the electrode. These data were compared with clinical data, including electrode system used, the number of years between implantation and death, type of tissue used at surgery, and the age and sex of the patients. RESULTS: The 21 specimens included cases implanted with the Symbion Ineraid, Cochlear Corporation Nucleus 22-channel, Cochlear Corporation Nucleus 24-channel, a Cochlear Corporation Nucleus single channel, and Advanced Bionics Clarion C1 devices. At the cochleostomy site, and just within the cochlea, there was a robust fibrous and bony tissue response in all 21 ears and in most cases, there was a fibrous sheath surrounding the electrode in the middle ear. No recognizable open communication or potential communication between the middle ear and the inner ear was seen in any of the 21 ears. An inflammatory cellular response, including mononuclear leukocytes, histiocytes, and foreign body giant cells, were present in 12 of the 21 temporal bones (57%) and was most intense at the cochleostomy site. No statistically significant relationship was found between the presence or absence of inflammatory cells and the type of tissue graft used at surgery. CONCLUSIONS: The histologic evidence presented in this study does not support open communication between the middle and the inner ear as part of the pathogenesis of bacterial meningitis as a late complication after cochlear implantation. Rather, the finding of a cellular inflammatory response in 12 of 21 temporal bones suggests that late hematogenous contamination and colonization of the implant is a much more likely pathogenic mechanism. This putative mechanism has implications for possible strategies to prevent meningitis after cochlear implantation.

Aged↗