Thomas J. Balkany

Vestibular effects of cochlear implantation.

Objectives/Hypothesis: Cochlear implantation (CI) carries with it the potential risk for vestibular system insult or stimulation with resultant dysfunction. As candidate profiles continue to evolve and with the recent development of bilateral CI, understanding the significance of this risk takes on an increasing importance.

Comparative Study of Cochlear Damage With Three Perimodiolar Electrode Designs

Objective To describe intracochlear insertion trauma caused by three perimodiolar cochlear implant electrodes.

Phase III clinical trial results with the Vibrant Soundbridge implantable middle ear hearing device: A prospective controlled multicenter study

OBJECTIVES : The goal of the study was to evaluate the performance of a semi-implantable middle ear hearing device (Vibrant Soundbridge System [VSB]; Symphonix Devices, Inc). STUDY DESIGN : A prospective, single-subject, repeated-measures multicenter study was conducted to determine the safety and efficacy of the VSB using analog and digital external processors. Measures included residual hearing, functional gain, speech recognition, acoustic feedback, occlusion, and patient self-assessment to determine satisfaction, perceived performance, and device preference compared with an appropriately fit acoustic hearing aid. Fifty-three adult subjects with moderate to severe sensorineural hearing loss were evaluated at 4 or more intervals after implantation. RESULTS : Improvements in satisfaction, performance, and preference were statistically significant with the VSB, as was functional gain across all test frequencies (P < 0.001). Occlusion and feedback were virtually eliminated. Aided speech recognition was comparable between VSB and the hearing aid. Residual hearing was unchanged. CONCLUSION : The VSB is a safe and effective treatment option for adults with moderate to severe sensorineural hearing loss.

Conservation of residual acoustic hearing after cochlear implantation.

Objective: This study was designed to test the hypothesis that partial hearing conservation is attainable after cochlear implantation with a long perimodiolar electrode. Surgical strategies for hearing conservation during cochlear implantation are described. Study design: Prospective, single-subject, repeated-measures design. Setting: Academic tertiary care center. Patients: Twenty-eight severely to profoundly hearing-impaired adult cochlear implant recipients who had some measurable hearing preoperatively. Intervention: Cochlear implantation using Nucleus Freedom Contour Advance electrode. Main Outcome Measures: Preimplant and postimplant pure-tone thresholds and speech recognition scores were obtained to determine the incidence and degree of conserved hearing at a mean interval of 9 (±3.9) months. Results: Thirty-two percent of subjects experienced complete conservation of hearing (0- to 10-dB loss), and 57% experienced partial conservation of hearing (>11 dB) after implantation. However, open-set speech recognition was partially conserved in only one subject. Cochlear implant performance was not better in patients with conservation of residual hearing. Conclusion: Conservation of pure-tone hearing was possible in 89% of implanted patients; however, residual speech perception was not conserved with this long perimodiolar electrode. A ceiling effect tends to inflate the prevalence of hearing conservation in implantation studies of severely to profoundly hearing-impaired patients.

Intratympanic Versus Intravenous Delivery of Methylprednisolone to Cochlear Perilymph

Objective: To compare methylprednisolone concentrations in the perilymph of the human ear and in plasma after intratympanic (IT) or intravenous (IV) administration. Methods: Methylprednisolone concentrations in the perilymph of patients during cochlear implantation were compared after 3 dosing strategies of methylprednisolone solution for injection (40 mg/ml): 1) IT administration of up to 40 mg was injected into the middle ear through the external auditory canal via a 27-gauge needle passed through a small anterosuperior myringotomy; 2) IV administration of 1 mg/kg was given as a single injection over 30 seconds; 3) IV administration of 10 mg/kg was infused over 30 minutes. Perilymph (single sample, ~20 μL) was sampled using a needle passed through the round window membrane, from 0.5 to 3 hours after dosing. In most patients, simultaneous blood sampling was performed. Methylprednisolone concentrations were measured by high-performance liquid chromatography with a limit of quantification of 0.001 mg/L. Results: In 39 patients studied, 33 perilymph samples were suitable for measurement, along with 26 plasma samples. Median perilymph concentrations were 6.7 mg/L (n = 18; range, 0.2-89.4 mg/L) after IT administration, 0.053 mg/L (n = 8; range, 0-0.47 mg/L) after IV injection of 1 mg/kg, and 0.2 mg/L (n = 7; range, 0.067-3.1 mg/L) after IV infusion of 10 mg/kg. The median perilymph concentrations were 126-fold higher after the IT administration than after 1 mg/kg IV (p = 0.0003) and 33-fold higher than after 10 mg/kg IV infusion (p = 0.0045). Plasma concentrations after IT administration were 16-fold lower than after IV administration of 1 mg/kg (p = 0.0006), and 136-fold lower than after IV infusion of 10 mg/kg (p = 0.0006). Conclusion: IT administration of methylprednisolone in humans results in much higher perilymph concentrations and much lower systemic concentrations than IV administration.

Hearing Loss in Down's Syndrome A Treatable Handicap More Common Than Generally Recognized

Significant hearing loss was found in about two-thirds of a series of 107 individuals with Downs syndrome. Hearing loss of that degree causes retarda tion of speech, language and intellectual development in normal children. Downs children are presumably affected even more by this sensory depriva tion and without correction are prevented from reaching their full potential.

Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population

Usher syndrome type I (USH1), the most severe form of this syndrome, is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. At least seven USH1 loci, USH1A-G, have been mapped to the chromosome regions 14q32, 11q13.5, 11p15, 10q21-q22, 21q21, 10q21-q22, and 17q24-25, respectively. Mutations in five genes, including MYO7A, USH1C, CDH23, PCDH15 and SANS, have been shown to be the cause of Usher syndrome type 1B, type 1C, type 1D, type 1F and type 1G, respectively. In the present study, we carried out a systematic mutation screening of these genes in USH1 patients from USA and from UK. We identified a total of 27 different mutations; of these, 19 are novel, including nine missense, two nonsense, four deletions, one insertion and three splicing defects. Approximatelly 35–39% of the observed mutations involved the USH1B and USH1D genes, followed by 11% for USH1F and 7% for USH1C in non-Acadian alleles and 7% for USH1G. Two of the 12 MYO7A mutations, R666X and IVS40-1G>T accounted for 38% of the mutations at that locus. A 193delC mutation accounted for 26% of CDH23 (USH1D) mutations, confirming its high frequency. The most common PCDH15 (USH1F) mutation in this study, 5601-5603delAAC, accounts for 33% of mutant alleles. Interestingly, a novel SANS mutation, W38X, was observed only in the USA cohort. The present study suggests that mutations in MYO7A and CDH23 are the two major components of causes for USH1, while PCDH15, USH1C, and SANS are less frequent causes.

Middle ear effusions in neonates

Suppurative middle ear effusions (MEE) have been shown to occur commonly in neonates. In spite of this, otoscopy is not routinely performed on septic infants in the neonatal intensive care unit (ICU). This is clinically significant since unrecognized suppurative MEE may act as a focus for dissemination of bacteria into the circulation and/or central nervous system (CNS).

Blocking c-Jun-N-terminal kinase signaling can prevent hearing loss induced by both electrode insertion trauma and neomycin ototoxicity.

Neomycin ototoxicity and electrode insertion trauma both involve activation of the mitogen activated protein kinase (MAPK)/c-Jun-N-terminal kinase (JNK) cell death signal cascade. This article discusses mechanisms of cell death on a cell biology level (e.g. necrosis and apoptosis) and proposes the blocking of JNK signaling as a therapeutic approach for preventing the development of a permanent hearing loss that can be initiated by either neomycin ototoxicity or electrode insertion trauma. Blocking of JNK molecules incorporates the use of a peptide inhibitor (i.e. D-JNKI-1), which is specific for all three isoforms of JNK and has been demonstrated to prevent loss of hearing following either electrode insertion trauma or loss of both hearing and hair cells following exposure to an ototoxic level of neomycin. We present previously unpublished results that control for the effect of perfusate washout of aminoglycoside antibiotic by perfusion of the scala tympani with an inactive form of D-JNKI-1 peptide, i.e. JNKI-1(mut) peptide, which was not presented in the original J. Neurosci. article that tested locally delivered D-JNKI-1 peptide against both noise- and neomycin-induced hearing loss (i.e. Wang, J., Van De Water, T.R., Bonny, C., de Ribaupierre, F., Puel, J.L., Zine, A. 2003a. A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J. Neurosci. 23, 8596-8607). D-JNKI-1 is a cell permeable peptide that blocks JNK signaling at the level of the three JNK molecular isoforms, which when blocked prevents the increases in hearing thresholds and the loss of auditory hair cells. This unique therapeutic approach may have clinical application for preventing: (1) hearing loss caused by neomycin ototoxicity; and (2) the progressive component of electrode insertion trauma-induced hearing loss.

Systematic approach to electrode insertion in the ossified cochlea

Ossification of the fluid spaces of the cochlea occurs often in candidates for cochlear implantation, especially children. When noted before surgery on computerized tomography, ossification previously was thought to contraindicate cochlear implantation because of possible mechanical obstruction and uncertainty about the level of function that could be achieved by stimulating an ossified cochlea. However, during the preceding 6 years, techniques have been developed that permit implantation in ossified cochleas. We present a systematic approach that has been developed to treat the three clinically important categories of cochlear ossification: round window niche obliteration, inferior segment obstruction, and upper segment obstruction. Case reports are presented for each of these three drill-out procedures, demonstrating results often similar to those expected for implantation of the nonossified cochlea.