GRM7 variants confer susceptibility to age-related hearing impairment.

Age-related hearing impairment (ARHI), or presbycusis, is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. Here we describe the results of the first whole genome association study for ARHI. The study was performed using 846 cases and 846 controls selected from 3434 individuals collected by eight centers in six European countries. DNA pools for cases and controls were allelotyped on the Affymetrix 500K GeneChip for each center separately. The 252 top-ranked single nucleotide polymorphisms (SNPs) identified in a non-Finnish European sample group (1332 samples) and the 177 top-ranked SNPs from a Finnish sample group (360 samples) were confirmed using individual genotyping. Subsequently, the 23 most interesting SNPs were individually genotyped in an independent European replication group (138 samples). This resulted in the identification of a highly significant and replicated SNP located in GRM7, the gene encoding metabotropic glutamate receptor type 7. Also in the Finnish sample group, two GRM7 SNPs were significant, albeit in a different region of the gene. As the Finnish are genetically distinct from the rest of the European population, this may be due to allelic heterogeneity. We performed histochemical studies in human and mouse and showed that mGluR7 is expressed in hair cells and in spiral ganglion cells of the inner ear. Together these data indicate that common alleles of GRM7 contribute to an individual's risk of developing ARHI, possibly through a mechanism of altered susceptibility to glutamate excitotoxicity.

Histopathologic assessment of fibrosis and new bone formation in implanted human temporal bones using 3D reconstruction.

OBJECTIVE: To evaluate new bone formation and fibrosis in implanted human temporal bones and relate that to neurosensory elements preservation. STUDY DESIGN: Human temporal bone histopathology study. SETTING: Temporal bone laboratory. SUBJECTS AND METHODS: Ten human temporal bones from eight patients with multichannel cochlear implants and one single-electrode implant were examined under light microscopy and reconstructed with AMIRA 4.1 3D reconstruction software. Volumes of new bone formation, fibrosis, and patent area were calculated in each bone. RESULTS: The amount of fibrosis and new bone formation postimplantation varied among bones. There were no statistically significant relationships between age at implantation or duration of implantation and the overall amount of new tissue in the implanted ear. There was a relationship between total amount of new tissue and preservation of neurosensory elements only in segment I of the cochlea (Rho=-0.75, P

The medial wall of the jugular foramen: a temporal bone anatomic study.

OBJECTIVE: To better understand the variable and complex anatomy of the jugular foramen (JF) and the relationship between the neurovascular structures in the medial wall of the jugular bulb (JB). STUDY DESIGN: A temporal bone anatomic study. SETTING: A temporal bone laboratory within a hearing research facility. SUBJECTS AND METHODS: Twenty-two temporal bones were dissected under the operating microscope. The JF anatomy was exposed by using the modified infratemporal fossa approach (no rerouting of the facial nerve). Pictures were taken at various intervals during the dissection. Distances between important structures were measured with two-point calipers and transferred to a millimetric scale. RESULTS: The right JF was found to be larger than the left side in 72.7 percent of the dissected temporal bones. A fibrous septum separated the glossopharyngeal (CN IX) from the vagus (CN X) and accessory (CN XI) nerves in 19 specimens (86.4%), and a complete bony septum was present in three specimens (13.6%). The CNs IX, X, and XI traveled anteromedially to the JB within the JF. The inferior petrosal sinus (IPS) drained into the medial wall of the JB at various locations by two or more channels. In most of the specimens (86.4%), the IPS separated CNs IX and X. CONCLUSION: The lower cranial nerves have an intimate relationship to the medial wall of the JB. Within the JF, the neurovascular structures vary in size, shape, and location. To minimize surgical morbidity, the surgeon should be familiar with the complex anatomy of the JB and its variations.

Single vertical incision for Baha implant surgery: preliminary results.

OBJECTIVES: A single vertical skin incision with subcutaneous tissue removal is a cosmetic alternative for Baha implant placement. We aimed to determine the preliminary complication rate using a 4-cm vertical skin incision. STUDY DESIGN: Retrospective review. SUBJECTS AND METHODS: Vertical incision Baha implant placements from January 2006 to August 2007 were reviewed. Complications including skin irritation, skin overgrowth, and implant extrusion were tallied. A total of 71 patients underwent surgery, with a mean follow-up time of 7 months. RESULTS: There were five minor complications (three cases of skin irritation, one wound infection requiring oral antibiotics, one postoperative hematoma) and seven major complications (one case of irritation requiring abutment removal, six cases of skin overgrowth or infection requiring flap revision), for a total complication rate of 16.9 percent. CONCLUSIONS: A single vertical incision for Baha implant placement has a complication rate similar to that of traditional dermatome use in this preliminary study. Patients with thick scalps or risk factors for hypertrophic scarring may require longer abutments.

Treatment of recurrent and residual glomus jugulare tumors.

Residual and recurrent glomus jugulare tumors are rare but challenging. Treatment options include microsurgical resection, stereotactic radiotherapy, a combination of modalities, and "observation." Choice of treatment must be made on a case-by-case basis, considering patient age, health status, location and size of tumor, status of the lower cranial nerves, and, of course, patient desire. Surgery is preferred when total resection of the tumor with preservation of function is deemed achievable. When function of the lower cranial nerves has been compromised, total surgical resection may also be possible, provided that the patient's health allows it. Cases where function is still preserved despite presence of a large tumor are more challenging, and a combination modality may be most effective. The goal of treatment is to provide tumor control with low morbidity. Current surgical techniques and the availability of stereotactic radiotherapy make this possible in the majority of cases.

Revision cochlear implant surgery in children.

OBJECTIVE: To determine the incidence of revision cochlear implant (CI) surgery in children and the indications for revision surgery and to examine the pattern of events that lead to revision CI surgery. STUDY DESIGN: Retrospective case review. SETTING: Two tertiary pediatric CI centers. PATIENTS: Pediatric CI patients who underwent revision surgery related to their CI. MAIN OUTCOME MEASURES: Reasons for revision, surgical outcomes, complications, performance, and device analyses were sought. RESULTS: Nine hundred fifty-two pediatric CI operations were performed between 1991 and 2005. Ninety-three patients underwent 107 (11.2%) revision operations. Hard device failure occurred in 46% (n = 49); soft failure occurred in 15% (n = 16); medical/surgical causes were responsible for 37% (n = 40); and magnet dislodgement requiring revision surgery occurred in 2% (n = 2). Head trauma was associated with 41% of the hard failure cases (n = 20). Device analyses revealed identifiable abnormalities in most of both hard and soft failure cases. In most patients, auditory performance equaled or surpassed the best preoperative performance by 6 to 12 months after revision. CONCLUSION: Revision CI surgery is common among pediatric CI recipients. Hard failure is the most common reason for undertaking revision surgery, and this mode of failure is frequently associated with preceding head trauma. Patients and parents should be counseled that performance is expected to equal or surpass the child's best level of performance before revision surgery, although this may take some time, and exceptions do exist.

Prevention and treatment of cerebrospinal fluid leak after translabyrinthine acoustic tumor removal.

OBJECTIVE: To determine the incidence rate of cerebrospinal fluid (CSF) leak after translabyrinthine acoustic tumor removal using titanium mesh cranioplasty and to compare with previous series and historical controls. STUDY DESIGN: Database analysis with historical controls. SETTING: Tertiary referral neurotologic private practice. PATIENTS: The series of 389 patients who underwent titanium mesh cranioplasty after translabyrinthine tumor removal between March 2003 and July 2005. The results were compared with those in a group of 1,195 translabyrinthine tumor removal patients from our previously published series and with those in a group of 324 patients from the immediately preceding two-year period. INTERVENTION: Cranioplasty using titanium mesh after acoustic tumor removal. MAIN OUTCOME MEASURES: Rates of CSF leak for this method and previous methods of closure. RESULTS: Thirteen patients (3.3%) had CSF leaks when using the new method of titanium mesh closure. This compares with rates of 10.9% and 8.7% in series in which other methods of closure were used (p < 0.001 and 0.003). The rates of CSF leak requiring reoperation were 0.5%, 2.5%, and 1.9% for the new and the two older series, respectively. CONCLUSION: In our hands, titanium mesh cranioplasty seems to reduce the rate of CSF leaks after the translabyrinthine removal of acoustic tumors.

Multichannel cochlear implants: relation of histopathology to performance.

OBJECTIVES: To determine the relationship of surviving neural elements to auditory function in multichannel cochlear implant temporal bones. STUDY DESIGN: Case series of all 14 existing multichannel cochlear implants in our temporal bone collection. METHODS: Devices included Nucleus 22 (n = 11), Nucleus 24 (n = 1), Ineraid (n = 1), and Clarion (n = 1). Morphologic evaluation of structural elements including spiral ligament, stria vascularis, hair cells, peripheral processes, and spiral ganglion cells was performed. Clinical performance data were obtained from patient charts. For eight patients, nonimplanted contralateral temporal bones were available and paired comparisons were made. RESULTS: Despite frequent absence of hair cells and peripheral processes, all bones had at least some remaining spiral ganglion cells. Percent of normal remaining structures were unrelated to auditory performance with the implant for any of the structural elements. Ganglion cell count in segment III showed significant negative correlations to speech discrimination scores for words and sentences (Rhos = -.687 and -.661, P < or = .03 and .04) as did segment IV and total ganglion cell count with word score (Rhos = -.632 and -.638; P < or = .05). Spiral ganglion cell survival did not differ between implanted and nonimplanted ears, with the exception of segment I, which had fewer cells in the implanted ear (P < or = .028). CONCLUSIONS: Performance variability of cochlear implants cannot be explained on the basis of cochlear neuronal survival. Although hair cells and peripheral processes were frequently absent or greatly diminished from normal, all subjects had at least some spiral ganglion cells. And, in this series, there was an inverse relationship between survival of ganglion cells and performance.

Human cochleae with three turns: an unreported malformation.

OBJECTIVE: The objective of this histologic study of archival temporal bone sections was to describe the morphology of human cochleae found with three turns, a previously unreported anomaly, found in three pairs of temporal bones. METHODS: The authors conducted histopathologic processing and measurement of basilar membrane length. Basilar membrane length was compared with that found in six normal control bones. RESULTS: Cochleae with three complete turns, rather than the usual two and a half turns, are described for the first time. All had longer than normal basilar membranes, with a mean length of 40.6 mm compared with a mean of 33.8 mm in the normal bones. CONCLUSIONS: Human cochleae with three turns exist as an unreported anomaly. This is a new category of anomaly, not likely based on interruption of development.

Distribution of low-frequency nerve fibers in the auditory nerve: Temporal bone findings and clinical implications.

HYPOTHESIS: Low-frequency cochlear fibers are on the outer surface of the auditory nerve adjacent to the vestibular nerve in the distal part of the internal auditory canal. BACKGROUND: There is a misconception that low-frequency cochlear fibers are in the core of the cochlear nerve and are surrounded by high-frequency fibers. METHODS: We analyzed temporal bones with a loss of upper spiral ganglion cells caused by different etiologies (n = 6) and traced the corresponding fibers into the distal internal auditory canal. Spiral ganglion cells for each segment (I-IV) of the cochlea were counted, and we defined the location of nerve fibers from the various segments. RESULTS: There was total or near-total degeneration of the upper spiral ganglion cells in these bones. Corresponding low-frequency fibers were on the outer surface of the cochlear nerve adjacent to the vestibular nerve in the distal segment of the internal auditory canal. CONCLUSION: Low-frequency fibers seem to be located at the periphery of the cochlear nerve. These findings provide one possible explanation for the low-frequency sensorineural hearing loss found in 10% of patients with vestibular nerve schwannomas and may have clinical relevance in the diagnosis of these lesions.

Clinical performance of children following revision surgery for a cochlear implant.

OBJECTIVES: The purpose of this study was to describe the causes for revision surgery and to compare clinical performance before and after surgery in children who required electrode reinsertion. STUDY DESIGN AND SETTINGS: Soundfield thresholds and speech recognition scores were compared before device failure and following electrode reinsertion. Temporal bones from a deceased adult implant user who underwent bilateral revision implantation were analyzed. RESULTS: Histopathology in the adult temporal bones revealed new bone formation in the scala tympani and substantially reduced spiral ganglion counts, with open-set speech recognition realized. Of 28 children undergoing revision surgery, 18 required electrode reinsertion. With the exception of 1 patient with severe cochlear malformation, new electrode arrays were fully inserted without difficulty. Clinical outcomes between pre-device failure and post-electrode reinsertion did not differ statistically. CONCLUSION AND SIGNIFICANCE: Electrode reinsertion is technically feasible in the pediatric population. The majority of children recover their prerevision clinical performance. EBM RATING: C-4.

Identification of target proteins involved in cochlear otosclerosis.

HYPOTHESIS: Investigation of differential protein expression will provide clues to pathophysiology in otosclerosis. BACKGROUND: Otosclerosis is a bone remodeling disorder limited to the endochondral layer of the otic capsule within the temporal bone. Some authors have suggested an inflammatory etiology for otosclerosis resulting from persistent measles virus infection involving the otic capsule. Despite numerous genetic studies, implication of candidate genes in the otosclerotic process remains elusive. We employed liquid chromatography-mass spectrometry (LC-MS) analysis on formalin-fixed celloidin-embedded temporal bone tissues for postmortem investigation of otosclerosis. METHODS: Proteomic analysis was performed using human temporal bones from a patient with severe otosclerosis and a control temporal bone. Sections were dissected under microscopy to remove otosclerotic lesions and normal otic capsule for proteomic analysis. Tandem 2D chromatography mass spectrometry was employed. Data analysis and peptide matching to FASTA human databases was done using SEQUEST and proteome discoverer software. RESULTS: TGFß1 was identified in otosclerosis but not in the normal control temporal bone specimen. Aside from TGFß1, many proteins and predicted cDNA-encoded proteins were observed, with implications in cell death and/or proliferation pathways, suggesting a possible role in otosclerotic bone remodeling. Immunostaining using TGFß1 monoclonal revealed marked staining of the spongiotic otosclerotic lesions. CONCLUSIONS: Mechanisms involved in cochlear extension of otosclerosis are still unclear, but the implication of TGFß1 is supported by the present proteomic data and immunostaining results. The established role of TGFß1 in the chondrogenesis process supports the theory of a reaction targeting the globulae interossei within the otic capsule.

Preliminary results with the use of AlloDerm in chronic otitis media.

OBJECTIVES/HYPOTHESIS: AlloDerm, an acellular dermal graft, has been used successfully as a material for soft tissue implantation. The authors report their experience with the use of AlloDerm in the reconstruction of the tympanic membrane. STUDY DESIGN: Case review study. METHODS: Charts were reviewed for all patients who underwent tympanoplasty with and without mastoidectomy between June 1999 and June 2002 in whom AlloDerm was used as a grafting material. There were 24 patients, 17 with simple perforations (8 revisions) and 7 with chronic otitis media with cholesteatoma (6 revisions). Success was defined as closure of the tympanic membrane perforation. RESULTS: Closure of the perforation using AlloDerm was achieved in 87.5% of the patients (ie, in all but three patients). Another patient developed serous otitis media and required a myringotomy tube in the postoperative period. CONCLUSIONS: The success rate for AlloDerm in tympanoplasty was similar to that of temporalis fascia in the authors' experience. AlloDerm can provide a suitable grafting material when fascia is not available or when the size of the defect precludes the use of fascia.

Cochlear implantation in children with otitis media.

OBJECTIVE: To describe the outcome of cochlear implantation in a cohort of pediatric patients with a history of otitis media. STUDY DESIGN: Retrospective chart review and follow-up phone survey. METHODS: The medical records of patients younger than 48 months of age who underwent cochlear implantation were reviewed for demographics, complications, and history of otitis media and bilateral myringotomy and ventilation tubes. A follow-up phone survey was performed to determine the long-term natural history of otitis media. RESULTS: The records of 126 profoundly deaf pediatric patients were reviewed. Seventy-two percent had a history of at least one episode of otitis media, 31% had a history of greater than three episodes, and 2% had a history of chronic serous otitis media. Twenty-three percent underwent bilateral myringotomy and tubes in the distant past, 6 to 8 weeks before implantation, at the time of implantation, or after implantation. A phone survey was successfully completed for 76 patients with a mean follow-up period of 46 months. There was a significant decrease in the incidence of otitis media after the cochlear implantation in the majority of patients with a history of otitis media with and without a history of bilateral myringotomy and tubes. CONCLUSIONS: Placement of ventilation tubes either before or at the time of cochlear implantation seems to adequately prevent infectious disease-related complications in otitis-prone children. Therefore, implantation should not be delayed, and subsequent episodes of otitis media can be managed by conventional therapy.

Facial nerve paralysis following cochlear implant surgery.

OBJECTIVES: Facial nerve paralysis is a rare but devastating complication of cochlear implant surgery. The aims of the study were to define the incidence of facial nerve paralysis in our series and understand possible mechanisms of injury. STUDY DESIGN: Retrospective chart review and case reports. METHODS: Charts were reviewed of all 705 patients implanted between 1980 and 2002 at the authors' institutions to identify those with postoperative facial nerve weakness and determine incidence. For patients with facial nerve weakness, onset, degree, and timing of paralysis were noted; clinical findings were correlated to operative report findings. The method of treatment was noted, and the final facial nerve function outcome was recorded. RESULTS: Five patients (one child and four adults) were found to have postoperative facial nerve weakness, for an incidence of 0.71%. This complication was delayed in all cases, ranging from 18 hours to 19 days postoperatively. All patients were treated with steroids or steroids combined with antiviral medication, and all ultimately recovered normal facial function. CONCLUSIONS: In the study series, the incidence of facial nerve paralysis following cochlear implant surgery was 0.71%. Possible mechanisms of injury included heating injury and viral reactivation. All patients presented with a delayed facial nerve paralysis and did recover normal facial nerve function.

Revision cochlear implant surgery: causes and outcome.

OBJECTIVE: To review experience with cochlear implant reimplantations, including effect of reinsertion on audiological performance. STUDY DESIGN AND SETTING: Retrospective review of cochlear implant reinsertions in patients seen in a private tertiary neurotologic practice. Forty-three patients (8 adults and 35 children) underwent revision cochlear implant surgery for device failure or upgrade. Findings at initial and repeat operations were noted, including number of electrodes inserted, and speech perception performance data were obtained when available. RESULTS: Five complications occurred in the reinsertion operations, 2 (6%) intraoperative cerebral spinal fluid leaks and 3 (7%) postoperative flap breakdowns with implant extrusion. Number of electrodes inserted was unchanged in 40/43 patients. Speech perception abilities remained stable or improved. CONCLUSION: Cochlear reimplantation is technically feasible and allows for continued auditory stimulation. SIGNIFICANCE: Patients facing reimplantation must be aware of the possibility of differences in sound quality and speech recognition performance with their replacement device, but speech perception ability will typically remain the same or improve.

Transcranial contralateral cochlear stimulation in unilateral deafness.

OBJECTIVES: The purpose of this study is to evaluate the effectiveness of Bone Anchored Cochlear Stimulator (BAHA) in transcranial routing of signal by implanting the deaf ear. Study design and settings Eighteen patients with unilateral deafness were included in a multisite study. They had a 1-month pre-implantation trial with a contralateral routing of signal (CROS) hearing aid. Their performance with BAHA was compared with the CROS device using speech reception thresholds, speech recognition performance in noise, and the Abbreviated Profile Hearing Benefit and Single Sided Deafness questionnaires. RESULTS: Patients reported a significant improvement in speech intelligibility in noise and greater benefit from BAHA compared with CROS hearing aids. Patients were satisfied with the device and its impact on their quality of life. No major complications were reported. Conclusion and significance BAHA is effective in unilateral deafness. Auditory stimuli from the deaf side can be transmitted to the good ear, avoiding the limitations inherent in CROS amplification.

Total ossiculoplasty: short- and long-term results using a titanium prosthesis with footplate shoe.

OBJECTIVES: Review experience using a titanium TORP with a footplate shoe; compare early and long-term hearing results and complications with those obtained using a TORP alone. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral neurotologic private practice. PATIENTS: Patients undergoing total ossicular replacement with a titanium prosthesis (total ossicular reconstruction prosthesis [TORP]); 74 with a TORP + footplate shoe and 62 with TORP alone. INTERVENTION: Ossicular chain reconstruction with a titanium TORP. MAIN OUTCOME MEASURES: Short- and long-term air-bone gap (ABG), change in ABG from preoperative to postoperative and from postoperative to last recorded follow-up, sensorineural hearing loss. RESULTS: The shoe group had a smaller mean postoperative ABG (17.7 dB versus 21.6 dB, p ≤ 0.048) and a greater average amount of closure in ABG (21.9 dB versus 13.2 dB, p ≤ 0.004), but there was no significant difference in percentage of patients achieving a postoperative ABG of 20 dB or lesser (57.4% versus 61.6%). There were no differences between groups at long-term follow-up or in amount of change in ABG from postoperative to last audiogram or in amount of change in sensorineural hearing from preoperative to postoperative. Although surgical factors (number of previous surgeries, and presence of a cavity) impacted outcomes, there were no interactions with prosthesis group and no differences in complications between groups. CONCLUSION: Ossicular reconstruction still presents challenges. A titanium prosthesis with a "shoe" for stabilization may offer advantages. Results in this study consistently favored the TORP + shoe group,although not all differences achieved statistical significance. A larger study might better define possible advantages of the shoe prosthesis for specific subgroups of patients.

Conservative management of vestibular schwannoma: expectations based on the length of the observation period.

OBJECTIVE: Evaluate long-term prevalence of tumor growth and need for further treatment in patients with a vestibular schwannoma treated with conservative management. STUDY DESIGN: Retrospective chart review. SETTING: Private neurotologic tertiary referral center. PATIENTS: Vestibular schwannoma patients undergoing conservative management and previously studied (N = 114). Mean time to last magnetic resonance imaging was 4.8 years and to last follow-up was 6.4 years (maximum, 18.5 yr). INTERVENTION: Serial gadolinium-enhanced magnetic resonance imaging with size measurement. MAIN OUTCOME MEASURES: Change in maximum tumor dimension of 2 mm or higher (growth), further treatment, audiologic measures-pure-tone average, word recognition, AAO-HNS (American Academy of Otolaryngology-Head and Neck Surgery) hearing class. RESULTS: Thirty-eight percent of tumors demonstrated growth; an average of 6.5 mm (SD, 3.8) at a mean rate of 3.1 mm per year. Of patients with no growth at 1 year or less, 20% grew by last follow-up. Overall, 31% had further treatment after a mean of 3.8 years (SD, 3.5; maximum, 18.5 yr). Of those followed for 5 to 10 years, 18% eventually had further treatment. Only 56% of growing tumors had further treatment by last follow-up; 14.8% with nongrowing tumors also had further treatment. Pure-tone average declined more in tumors that grew (mean Δ = 28.8 dB) than those that did not (mean Δ = 16.5 dB) (p ≤ 0.025), but there was no correlation between the amount of change in hearing and in the size of the tumor. Of patients with an initial AAO-HNS hearing Class A, 85.7% retained serviceable hearing. CONCLUSION: For patients electing an observation approach to treatment of vestibular schwannoma, about 31% may eventually undergo further treatment. Of those followed for 5 to 10 years, 18% eventually had further treatment. However, some patients are followed with radiologic evaluations for many years without necessity for further treatment.