Simon I. Angeli

Biopolymer-released dexamethasone prevents tumor necrosis factor α-induced loss of auditory hair cells in vitro: Implications toward the development of a drug-eluting cochlear implant electrode array

Hypothesis: Polymer-eluted dexamethasone (DXM) will retain its ability to protect against tumor necrosis factor &agr; (TNF&agr;)-induced hair cell (HC) loss. Background: TNF&agr; has been shown to be associated with trauma-induced hearing loss. DXM has been demonstrated to protect the cochlea against trauma-induced hearing loss. DXM is currently administered either systemically or locally to treat patients with sudden hearing loss of unknown cause. Methods: P-3 organ of Corti explants challenged with an ototoxic level of TNF&agr; was the experimental system, and the base form of DXM (DXMb) incorporated into a biorelease polymer (i.e., SIBS) was the otoprotection molecule tested. The efficacy of otoprotection was determined by counts of fluorescein isothiocyanate-phalloidin-stained HCs and changes in gene expression. Results: HC counts show 1) SIBS alone did not protect HCs from TNF&agr; ototoxicity (SIBS versus SIBS + TNF&agr;; p < 0.001), and 2) SIBS with DXMb provides a significant level of protection against TNF&agr;-induced loss of HCs (TNF&agr; + SIBS versus TNF&agr; + SIBS/DXMb, 299 &mgr;g; p < 0.001). Gene expression results show that polymer-eluted DXMb 1) upregulates antiapoptotic genes (i.e., Bcl-2, Bcl-xl) and downregulates a proapoptotic gene (i.e., Bax) in TNF&agr;-challenged explants and 2) downregulates TNFR1 in these explants. Conclusion: Polymer-eluted DXMb retains its otoprotection capabilities in our in vitro test system of TNF&agr;-challenged organ of Corti explants by altering the pattern of gene expression to favor survival of TNF&agr;-exposed HCs. These results, although in vitro, support the application of polymer containing DXMb to electrode arrays for the conservation of hearing during cochlear implantation.

The transcochlear approach revisited

Objective To evaluate the indications for, techniques used in, and patient outcomes after surgery with the transcochlear approach in the treatment of petroclival tumors. Methods Retrospective review of 24 cases between 1985 and 1995 at the House Ear Clinic (Los Angeles, CA, U.S.A.). Results Meningioma was the most common tumor. Complete removal was achieved in 82% of tumors after one-or two-stage surgeries (average follow-up time, 36 months). The second-stage surgery was a middle fossa transpetrous approach. Most patients had some degree of facial nerve dysfunction immediately after surgery, and 12 of 20 patients subsequently improved to House-Brackmann Grade III or better. Fifty-nine percent of patients had permanent neurologic sequelae because of either the surgery or their disease. Conclusion The transcochlear approach is best suited to treating petroclival intradural tumors that extend ventrally to the brainstem in patients without serviceable hearing. Temporary facial weakness is expected as a result of posterior facial nerve transposition.

Primary lymphoma of the internal auditory canal. Case report and review of the literature.

We report a rare case of a primary intracranial B cell lymphoma originating in the internal auditory canal. The clinical manifestations were indistinguishable from those of other, more common tumors of the same region. We achieved total gross tumor removal with preservation of the facial nerve. A detailed histologic examination and a systemic workup confirmed the primary nature of this tumor. To our knowledge, this is the second case reported in the literature of a primary malignant lymphoma originating in the internal auditory canal. This is the first instance that includes immunohistochemical and cytometric studies of fresh tissue. We discuss the management of primary lymphomas of the central nervous system, with special emphasis on their association with acquired immunodeficiency syndrome and other immune system diseases. Awareness of primary central nervous system lymphomas is important, since a greater occurrence of these rare tumors in the cerebellopontine angle is probable in the future.

Outcomes after surgical resection of head and neck paragangliomas: a review of 61 patients.

We reviewed the postoperative functional outcome following surgical resection of paragangliomas in patients with and without preoperative cranial nerve dysfunction. Patients who underwent surgical resections of head and neck paragangliomas were reviewed with functional outcomes defined as feeding tube and/or tracheostomy dependence, need for vocal cord medialization, and incidence of cerebral vascular accidents as primary end points. Secondary end points included pre- and postoperative function of lower cranial nerves and the impact of this dysfunction on long-term functional status. Sixty-one patients were identified: 27 with carotid paraganglioma (CP), 21 with jugular paraganglioma (JP), 8 with tympanic paragangliomas, 4 with vagal paragangliomas (VPs), and 1 with aortopulmonary paraganglioma. Following resection, 8 patients were feeding tube dependent, 14 patients required vocal cord medialization, 2 patients suffered strokes, but no patients required tracheostomy tubes. Twenty percent of patients (4/20) with JP and postoperative cranial neuropathies were feeding tube dependent, and 80% of patients (4/5) with CP and postoperative cranial nerve dysfunction were feeding tube dependent. Cranial nerve deficits were more common in patients with JP relative to those with CP. However, when cranial nerve dysfunction was present, our patients with CP had a higher incidence of temporary feeding tube dependence. Overall, 98% of patients were able to resume oral nutrition.

Differences in cochlear nerve cross-sectional area between normal hearing and postlingually deafened patients on MRI

Objectives. To demonstrate that parasagittal constructive interference in steady state (CISS) magnetic resonance imaging (MRI) can be used to accurately measure cochlear nerve cross-sectional area and thereby evaluate for statistically significant differences in the cochlear nerve cross-sectional areas of postlingually deafened and normal-hearing adults. Study Design. Cross-sectional study. Setting. Tertiary care medical center. Subjects and Methods. Parasagittal CISS MRIs of postlingually profoundly deafened cochlear implant candidates and normal-hearing patients at a tertiary care academic medical center between 2006 and 2009 were retrospectively identified. Two independent and blinded investigators measured the cochlear nerve height and width and calculated the cross-sectional area [π(H/2)(W/2)] at the fundus of the internal auditory canals. Measurements of both investigators were analyzed for reliability and agreement with an Altman plot, and deafened patient measurements were compared with results of the normal-hearing patients via Wilcoxon rank sum tests. Results. The cochlear nerve cross-sectional area of postlingually deafened patients (mean ± SD = 0.61 ± 0.16 mm2) was less than normal-hearing patients (0.94 ± 0.28 mm2). The difference was statistically significant (P = .002). There was good agreement between independent observer measurements. Conclusion. Parasagittal CISS MRI can be used to measure the cochlear nerve with good interobserver agreement, and there is a significant difference between the cross-sectional area of postlingually deafened and normal-hearing adults. The cross-sectional area may correlate with residual spiral ganglion cells and provide a prognostic indicator for post–cochlear implant performance, which is the focus of our ongoing research.

Postoperative validation of bone-anchored implants in the single-sided deafness population.

Objective The purpose of this study was to present objective and subjective outcomes on speech-in-noise testing as a predictor of patient performance after bone-anchored implant surgery in patients with single-sided deafness (SSD). Design Retrospective review of adult subjects who received bone-anchored implants for the indication of SSD comparing results on speech-in-noise measures in the unaided condition to postoperative aided condition using the patient’s external bone-anchored implant processor as a validation of device performance. Setting Tertiary referral center providing outpatient surgical and audiologic care. Patients Adult English speaking subjects with SSD who underwent bone-anchored implantation between 2005 and 2010. Intervention Subjects were evaluated with speech-in-noise measures in the sound field using a 90/270 speaker configuration in both the unaided and aided implant condition for validation of implant performance. Subjective benefit was evaluated using the Glasgow Hearing Aid Benefit Profile. Main Outcome Measures Outcome measures included signal-to-noise ratio (SNR) loss and word recognition ability in noise as measured using the QuickSIN and the Glasgow Hearing Aid Benefit Profile. Results A significant improvement in speech-in-noise measures was noted in the postoperative aided condition when compared with the unaided condition (Wilcoxon signed-rank test, p < 0.0001). Significant decrease in disability postoperatively also was observed (Wilcoxon signed-rank test, p < 0.001). Positive associations were observed for postoperative aided SNR loss and benefit, satisfaction, and use. Passing-Bablok regression analysis showed the preoperative and postoperative results to be statistically equivalent. Conclusion The results support the use of speech-in-noise measures as an accurate postimplantation assessment of overall benefit in patients with SSD. SNR loss is a good predictor of postoperative subjective benefit and satisfaction.

Injectable form of cross-linked hyaluronan is effective for middle ear wound healing.

Objectives: Two studies were designed to investigate a hyaluronan (HA) gel for middle ear (ME) wound healing. Methods: We used a guinea pig model of ME wound healing. In a long-term study, we performed a comparison of hearing and ME inflammation in 3 groups. Group 1 (n = 8) underwent bilateral wounding of ME mucosa and unilateral packing of the ME with HA gel (Sepragel). Group 2 (n = 6) was the same as group 1 except that the packing was absorbable bovine collagen sponges (Gelfoam). Group 3, the control group (n = 14), had operated, unpacked ears. In a short-term study, we investigated ME retention of HA gel at 1 and 2 weeks (n = 16). Results: At 1 week, all ears showed decreased distortion product otoacoustic emissions (DPOAEs) and auditory brain stem responses (ABRs) secondary to ME packing and postsurgical inflammation. The controls recovered preoperative DPOAEs and ABRs by week 2. Group 1 had decreased low-frequency DPOAEs at weeks 2 and 6, but their high-frequency DPOAEs and ABRs recovered to preoperative values by week 6. Group 2 had hearing losses that persisted throughout the study. Group 1 showed normal ME and inner ear histologic characteristics. Group 2 showed inflammatory cells within the ME and cochleas. Group 1 showed less packing retention than did group 2 at week 6 (p = 016). Eighty-five percent of the HA packing remained at 1 week, and 73% at 2 weeks. Conclusions: Hyaluronan gel was a relatively safe and effective ME packing material in our animal model.

Ethnic disparity in skin complications following bone-anchored hearing aid implantation.

Objectives Sound processor loading after implantation of a bone-anchored hearing aid is often delayed by skin-site complications. This study examined the frequency of skin-site complications in various ethnic groups and determined factors that may lead to higher rates of skin-site complications resulting in delayed processor loading. Methods Adult, English-speaking patients who underwent implantation of a bone-anchored hearing aid between 2007 and 2010 were reviewed. Demographic data including ethnicity, tobacco use, diabetes mellitus, immunosuppression, and long-term steroid use were determined. Major and minor skin-site complications and the time to processor loading were recorded. Results The mean time to processor loading was 9.5 weeks, and the mean follow-up time was 23 months. There were no cases of osseointegration failure. African American patients had a significantly higher rate of major skin-site complications (p < 0.005) and a longer time to processor loading (mean, 17.6 weeks; p < 0.05) than the other ethnic groups. There was no significant difference in minor skin complication rates. There was no correlation between diabetes mellitus, long-term immunosuppression, or tobacco use and skin-site complications. Conclusions Skin complications can delay processor loading following implantation of a bone-anchored hearing aid. There is a higher rate of major skin-site complications in African American patients, and these often delay processor loading. The risk of skin-site complications is not correlated with smoking, diabetes mellitus, or immunosuppression. An increased risk of skin-site complications is an important consideration for preoperative counseling.

Influence of DFNB1 status on expressive language in deaf children with cochlear implants.

Objective The objective of this study was to compare the language growth of children with connexin-related deafness (DFNB1) who received cochlear implants versus the language growth of implanted children with non-DFNB1 deafness. Study Design A prospective longitudinal observational study and analysis. Setting Two tertiary referral centers. Patients There were 37 children with severe-to-profound hearing loss who received cochlear implants before the age of 5 years. Interventions A standardized language measure, the section for expressive language of the Reynell Developmental Language Scale was used to assess expressive language skills at 2 times postimplantation (14 and 57 mo postimplantation). Molecular screening for DFNB1 gene variants. Main Outcome Measures Language quotient (LQ) scores (i.e., age-equivalent score obtained on the Reynell Developmental Language Scale divided by the child’s chronological age), results of genotyping. Results The mean language age at the second time interval (mean ± standard deviation, 51.8 ± 13 mo) was greater than at the first testing session (mean ± standard deviation, 19 ± 8 mo, p < 0.001, Wilcoxon signed rank test). When divided by genotype, DFNB1 children exhibited a higher LQ and less variability in scores than non-DFNB1 children at the second testing interval (Wilcoxon sign rank test, p = 0.0034). A regression analysis (linear-fit by least squares) conducted on 26 children with preimplantation audiometric data showed that DFNB1 status was the independent variable with greater predictive effect on LQ at the second testing interval, followed by age at implantation (R2 = 0.35, p = 0.0479). Conclusion Deaf children who received cochlear implants before the age of 5 years and use oral communication show substantial improvement in language abilities. In this study, DFNB1 children who use cochlear implants show greater gains in expressive language than non-DFNB1 children, independent of residual hearing, age at implantation, and duration of implant use.

Indium 111-labeled white blood cell scintigraphy as an unreliable indicator of malignant external otitis resolution

The field of otolaryngology-head and neck surgery has seen many advances in the treatment and prognosis of malignant external otitis (MEO). However, establishing the resolution of the infection remains problematic. A recent report suggests that indium 111-labeled white blood cell scintigraphy may be a reliable and timely indicator of resolution of infection. We present a case of a false-negative white blood cell scan in a patient with persistent MEO. A discussion of this case and a review of the literature illustrate that there continues to be no “gold standard” for establishing MEO resolution.