Cochlin isoforms and their interaction with CTL2 (SLC44A2) in the inner ear.

Choline transporter-like protein 2 (CTL2) is a multi-transmembrane protein expressed on inner ear supporting cells that was discovered as a target of antibody-induced hearing loss. Its function is unknown. A 64 kDa band that consistently co-precipitates with CTL2 from inner ear extracts was identified by mass spectroscopy as cochlin. Cochlin is an abundant inner ear protein expressed as multiple isoforms. Its function is also unknown, but it is suspected to be an extracellular matrix component. Cochlin is mutated in individuals with DFNA9 hearing loss. To investigate the CTL2-cochlin interaction, antibodies were raised to a cochlin-specific peptide. The antibodies identify several cochlin polypeptides on western blots and are specific for cochlin. We show that the heterogeneity of the cochlin isoforms is caused, in part, by in vivo post-translational modification by N-glycosylation and, in part, caused by alternative splicing. We verified that antibody to CTL2 co-immunoprecipitates cochlin from the inner ear and antibody to cochlin co-immunoprecipitates CTL2. Using cochlear cross-sections, we show that CTL2 is more widely distributed than previously described, and its prominent expression on cells facing the scala media suggests a possible role in homeostasis. A prominent but previously unreported ribbon-like pattern of cochlin in the basilar membrane was demonstrated, suggesting an important role for cochlin in the structure of the basilar membrane. CTL2 and cochlin are expressed in close proximity in the inner sulcus, the spiral prominence, vessels, limbus, and spiral ligament. The possible functional significance of CTL2-cochlin interactions remains unknown.

Pediatric cochlear implant patient performance as a function of age at implantation.

OBJECTIVE: The objective of this study was to examine the effect that age at implantation has on performance of children who received multichannel cochlear implants. STUDY DESIGN: This is a retrospective study of 295 children who were broken down into 5 age groups based on age at implantation: 1-3 years, 3-5 years, 5-7 years, 7-9 years, and 9-11 years. Speech perception test scores obtained 12, 24, and 36 months postactivation were compared for the 5 groups using repeated-measures analysis of variance. SETTING: This study was carried out at a tertiary academic medical center. PATIENTS: Subjects consisted of 295 children who ranged in age from 12 months to 10 years 11 months at the time they obtained their cochlear implant. INTERVENTION: All patients received their cochlear implant at a single implant facility. MAIN OUTCOME MEASURES: Performance on several speech perception tests was compared 12, 24, and 36 months postactivation. Performance was evaluated as a function of age at implantation. RESULTS: Patients in all 5 groups demonstrated improved scores when compared with scores obtained preoperatively with hearing aids. Repeated-measures analysis of variance (ANOVA) revealed a significant group by time interaction for 3 of the 5 measures. For all three of these measures, children implanted at younger ages demonstrated greater gains in speech perception over time than children implanted at older ages. CONCLUSIONS: These results are in agreement with those of previous studies indicating that early implantation facilitates improved development of speech perception skills in profoundly deaf children.

Antibodies to HSP-70 in normal donors and autoimmune hearing loss patients.

OBJECTIVE: To evaluate serum antibody to heat shock protein (HSP) 70 as a marker for autoimmune sensorineural hearing loss (AISNHL). DESIGN: Sera from 20 patients with rapidly progressive sensorineural HL and 20 control volunteers without HL were tested for antibody reactivity against multiple HSP 70 substrates. Substrates included recombinant human HSP (rHuHSP) 72, purified bovine brain heat shock cognate (HSC) 73 and HSP 72, as well as heat-shocked and non-heat-shocked protein extracts from bovine kidney (MDBK) cells. All serum donors were previously tested for antibody to guinea pig inner ear supporting cells; 17 of 20 patients but none (0 of 20) of the controls were positive. METHODS: Sera were tested using Western blots. RESULTS: Reactivity with rHuHSP 70 was observed in 16 patients and 17 controls. Similarly, 15 of 20 patients and 17 of 20 controls stained for both HSP 72 and HSC 73 from the bovine brain. When tested against the heat-shock-induced and control MDBK extracts, six patients and nine controls had greater reactivity with the induced HSP 72. CONCLUSION: The frequency of antibodies to HSP substrates did not differ in patients and controls. Prior studies reported that HSP 72 is the 68 kD antigen commonly detected by AISNHL sera. However, we show that HSP 72 antibodies are no more prevalent in patients than in normal controls. Thus, it is unlikely that the 68 kD protein is HSP 72. Therefore, HSPs are not appropriate substrates for serodiagnosis of AISNHL.

Implantation of the malformed cochlea.

OBJECTIVE: This study assesses the results of cochlear implantation in children with cochlear malformations. STUDY DESIGN: Retrospective, matched-pairs analysis of prospectively collected data. SETTING: University-based regional cochlear implant center. PATIENTS: Seventeen children with osseous cochlear malformations who had undergone implantation were matched and compared with a group of children with normal cochleae who had undergone implantation. INTERVENTIONS: All subjects received a multichannel cochlear implant and habilitation. MAIN OUTCOME MEASURES: All subjects were tested with the Early Speech Perception test, and the Glendonald Auditory Speech Perception tests for words and sentences. Patients were classified in a standardized speech perception category based on performance on the Early Speech Perception test. RESULTS: All subjects demonstrated improving performance on all measures of speech perception over time. Overall, the two groups showed no statistically significant differences in performance at 6 and 24 months. However, subjects with malformed cochleae evidenced slower rates of improvement than did their matched control subjects. Subjects with more severe malformations demonstrated poorer performance, but this may have been attributable to preoperative factors rather than to implant performance. CONCLUSIONS: Children with radiographic cochlear malformations benefit from cochlear implantation with multichannel devices. They ultimately perform as well as their matched counterparts with normal cochleae, although they may improve more slowly over time.

Hearing rehabilitation using the BAHA bone-anchored hearing aid: results in 40 patients.

OBJECTIVE: This study evaluates the U.S. experience with the first 40 patients who have undergone audiologic rehabilitation using the BAHA bone-anchored hearing aid. STUDY DESIGN: This study is a multicenter, nonblinded, retrospective case series. SETTING: Twelve tertiary referral medical centers in the United States. PATIENTS: Eligibility for BAHA implantation included patients with a hearing loss and an inability to tolerate a conventional hearing aid, with bone-conduction pure tone average levels at 60 dB or less at 0.5, 1, 2, and 4 kHz. INTERVENTION: Patients who met audiologic and clinical criteria were implanted with the Bone-Anchored Hearing Aid (BAHA, Entific Corp., Gothenburg, Sweden). MAIN OUTCOME MEASURES: Preoperative air- and bone-conduction thresholds and air-bone gap; postoperative BAHA-aided thresholds; hearing improvement as a result of implantation; implantation complications; and patient satisfaction. RESULTS: The most common indications for implantation included chronic otitis media or draining ears (18 patients) and external auditory canal stenosis or aural atresia (7 patients). Overall, each patient had an average improvement of 32+/-19 dB with the use of the BAHA. Closure of the air-bone gap to within 10 dB of the preoperative bone-conduction thresholds (postoperative BAHA-aided threshold vs. preoperative bone-conduction threshold) occurred in 32 patients (80%), whereas closure to within 5 dB occurred in 24 patients (60%). Twelve patients (30%) demonstrated 'overclosure' of the preoperative bone-conduction threshold of the better hearing ear. Complications were limited to local infection and inflammation at the implant site in three patients, and failure to osseointegrate in one patient. Patient response to the implant was uniformly satisfactory. Only one patient reported dissatisfaction with the device. CONCLUSIONS: The BAHA bone-anchored hearing aid provides a reliable and predictable adjunct for auditory rehabilitation in appropriately selected patients, offering a means of dramatically improving hearing thresholds in patients with conductive or mixed hearing loss who are otherwise unable to benefit from traditional hearing aids.

Speech, vocabulary, and the education of children using cochlear implants: oral or total communication?

This study examines the relationship between the teaching method, oral or total communication, used at children's schools and children's consonant-production accuracy and vocabulary development over time. Children who participated in the study (N = 147) demonstrated profound sensorineural hearing loss and had used cochlear implants for between 6 months and 10 years. Educational programs that used an oral communication (OC) approach focused on the development of spoken language, whereas educational programs that used a total communication (TC) approach focused on the development of language using both signed and spoken language. Using Hierarchical Linear Modeling (HLM) we compared the consonant-production accuracy, receptive spoken vocabulary, and expressive spoken and/or signed vocabulary skills, over time, of children who were enrolled in schools that used either OC or TC approaches, while controlling for a number of variables. These variables included age at implantation, preoperative aided speech detection thresholds, type of cochlear implant device used, and whether a complete or incomplete active electrode array was implanted. The results of this study indicated that as they used their implants the children demonstrated improved consonant-production accuracy and expressive and receptive vocabulary over time, regardless of whether their school employed a TC or OC teaching method. Furthermore, there appeared to be a complex relationship among children's performance with the cochlear implant, age at implantation, and communication/teaching strategy employed by the school. Controlling for all variables, children in OC programs demonstrated, on average, superior consonant-production accuracy, with significantly greater rates of improvement in consonant-production accuracy scores over time compared to children in TC programs. However, there was no significant difference between OC and TC groups in performance or rate of growth in consonant-production accuracy when children received their implants before the age of 5 years. There was no significant difference between the OC and TC groups in receptive spoken vocabulary scores or in rate of improvement over time. However, children in the TC group achieved significantly higher receptive spoken vocabulary scores than children in the OC group if they received their implant before the age of 5 years. The TC group demonstrated superior scores and rates of growth on the expressive vocabulary measure (spoken and/or signed) when compared to the OC group if they received their implants during their preschool or early elementary school years. There was no significant difference if the children received their implants during middle elementary school. Regardless of whether children were in the OC or TC group, children who received their implants during preschool demonstrated stronger performance, on average, on all measures over time than children who received their implants during their elementary school years. The results of this study suggest that children may benefit from using cochlear implants regardless of the communication strategy/teaching approach employed by their school program and that other considerations, such as the age at which children receive implants, are more important. Implications and future research needs are discussed.

Recurrence of acoustic neuroma after incomplete resection.

OBJECTIVE: To determine the risk of recurrent tumor in patients after incomplete resection of acoustic neuroma. STUDY DESIGN: Retrospective case review. SETTING: A tertiary referral center. PATIENTS: Thirty-nine patients were identified who underwent incomplete resection of acoustic neuroma between January 1988 and December 1993, and had a minimum follow-up of 3.5 years, at a mean of 6.2 years (range 3.5-10.2 years). INTERVENTION: Regular follow-up. using either computed axial tomography or magnetic resonance imaging yearly. MAIN OUTCOME MEASURES: Growth of residual tumor as determined by the increase in its greatest dimension on follow-up imaging studies and the necessity for additional treatment. RESULTS: Tumor regrowth occurred in 17 patients (44%). Ten patients (26%) required additional treatment during the follow-up period. CONCLUSION: This study suggests that incomplete resection of acoustic neuroma is associated with a significant risk of recurrent tumor requiring subsequent intervention.

Minimizing wound complications in cochlear implant surgery.

OBJECTIVE: An extended postauricular incision has replaced the standard C-shaped scalp flap for cochlear implant surgery at our institution. The postoperative wound complication rates of the two incisions were evaluated. STUDY DESIGN: This study was a retrospective case review. SETTING: This study was performed in a tertiary referral center. PATIENTS: A total of 256 adult and pediatric patients who underwent cochlear implantation during a 10-year period (1986 to 1996) were reviewed. MAIN OUTCOME MEASURE: Postoperative wound complications were identified. Major complications included flap necrosis, wound dehiscence with or without implant exposure, and wound infection requiring hospitalization. Hematoma, seroma, or superficial wound infections were considered minor complications. RESULTS: There were 6 major and 6 minor complications among 116 patients with the standard scalp flap (complication rate, 10.3%). There was only 1 minor complication among 140 implants using the postauricular incision (0.7%). CONCLUSION: The extended postauricular incision appears to significantly reduce the incidence of wound complications in cochlear implant surgery.

Disability from vestibular symptoms after acoustic neuroma resection.

OBJECTIVE: This study aimed to evaluate the recovery of balance function after acoustic neuroma resection. STUDY DESIGN: This study was a retrospective case review with patient survey. SETTING: The surgery was conducted at a tertiary referral center. PATIENTS: Patients who underwent surgical resection of acoustic neuroma and had preoperative vestibular function testing were eligible for entering the study. INTERVENTIONS: All patients received surgical resection of acoustic neuroma. Patients treated since 1990 received postoperative vestibular habituation exercises. MAIN OUTCOME MEASURES: These included postoperative symptom and disability scores, dizziness handicap inventory (DHI) total and subset scores, time after surgery at which patients were able to walk independently, whether patients returned to their usual professional responsibility, and time to return to full activities at work. RESULTS: Significant correlation was found between several preoperative symptoms and vestibular testing results and the resulting postoperative disability from dizziness. CONCLUSIONS: This information may be helpful in counseling patients before surgery with respect to the degree of postoperative dysequilibrium and may suggest that the clinician should initiate more aggressive vestibular rehabilitation exercises in patients who may be at greater risk of having persistent dysequilibrium develop after surgery.

Diagnostic testing for endolymphatic hydrops.

The development of a sensitive and specific diagnostic test for endolymphatic hydrops has eluded investigators for over 30 years. The absence of such a test has hampered basic and clinical research into Meniere's disease and related entities. Presently used tests are limited in their applicability because of their low sensitivity and specificity and a poor understanding of the underlying physiologic principles. Despite this, it is generally agreed that some of these studies have merit in selected situations. This article reviews the present state of diagnostic testing for endolymphatic hydrops. The use of nonspecific studies, such as basic audiometry and tests for recruitment, and "specific" studies, such as electrocochleography and dehydration testing, are critically reviewed.

Human autoantibodies and monoclonal antibody KHRI-3 bind to a phylogenetically conserved inner-ear-supporting cell antigen.

Autoimmunity is thought to be one cause of sensorineural hearing loss (SNHL). Sera from patients with rapidly progressive hearing loss have been shown to contain antibodies to a 68-kD protein in heterologous inner-ear tissue. Using guinea pig inner-ear tissue as the antigenic substrate and either Western blot or immunofluorescence (IF) or both, we tested sera from 74 patients suspected to have autoimmune hearing loss for inner-ear antibodies. Sera from 73 patients were tested by Western blot, and sera from 36 were tested by IF. Thirty-seven of 73 (51%) had antibody to a 68-70-kD protein by Western blot. Sera positive by IF stained supporting cells with a staining pattern like that previously observed with the KHRI-3 monoclonal antibody. There was concordance between Western blot and IF assays. Of 36 patients tested by both assays, 29/31 (94%) that were positive in Western blot were also positive by IF, three were negative by both tests, and two each were positive by one assay but negative by the other. Absorption of patient sera with human inner-ear tissue removed antibody reactivity to the guinea pig supporting cells, indicating that the antigen detected by the autoantibody is also present in the human inner ear. Absorption with an equal volume of white or red blood cells from the tissue donor did not remove the antibody reactivity to inner ear, showing that the absorption by inner-ear tissue is specific. Sera from three patients positive in both assays also stained a 68-70-kD inner-ear protein immunoprecipitated by the KHRI-3 monoclonal antibody, indicating that the monoclonal and human antibodies recognize the same antigen. The results support the hypothesis that patients with autoimmune sensorineural hearing loss produce autoantibodies to an inner-ear supporting cell antigen that is phylogenetically conserved and defined by the murine monoclonal antibody KHRI-3. Since KHRI-3 can induce hearing loss after infusion into the inner ear, it is likely that autoantibodies with the same antigenic target are also pathogenic in humans.

Predicting neuroradiologic outcome in patients referred for audiovestibular dysfunction.

PURPOSE: To relate clinical presentation and results of audiovestibular testing to neuroradiologic outcome in patients with audiovestibular dysfunction. METHODS: We retrospectively reviewed the neuroimaging studies, results of audiometric and vestibular testing, and medical records of 118 patients referred for imaging over a 2-year period for evaluation of sensorineural hearing loss, dizziness, and/or vertigo, and to rule out acoustic neuroma. Patients' presentation and results of audiometric and vestibular testing were associated with either a positive or negative neuroimaging outcome. Discriminant analysis was performed to identify variables related significantly to imaging results. Two-way cross-tabulation of these significant variables was performed to assess their sensitivity and specificity in predicting imaging outcome. RESULTS: Fifteen (13%) of 118 patients had neuroimaging findings related to presenting symptoms. Discriminant analysis identified vertigo, dizziness, and dysequilibrium as corresponding to negative radiologic outcome. Nonvestibulocochlear cranial nerve involvement correlated significantly with positive neuroimaging results. Of all audiovestibular testing, only vestibular testing results correlated significantly with neuroimaging outcome. In conjunction with the results of vestibular testing the symptoms and signs identified above yielded a sensitivity of 57% and specificity of 93% in predicting neuroradiologic results. In the absence of vestibular testing, sensitivity and specificity were 29% and 98%, respectively. CONCLUSIONS: Clinical presentation and audiovestibular testing could not sensitively predict the outcome of neuroimaging in our cohort of patients referred for audiovestibular dysfunction.

Promontory stimulation following translabyrinthine excision of acoustic neuroma with preservation of the cochlear nerve.

Promontory stimulation is an accurate method of assessing the functional integrity of the cochlear nerve by electrical stimulation. This technique is widely used in screening prospective candidates for cochlear implants. Recent reports have confirmed the integrity of cochlear nerve responses to electrical stimulation following labyrinthectomy and unsuccessful hearing preservation attempt by the retrosigmoid approach. In this report, the authors present three patients with intracanalicular acoustic neuromas excised through a translabyrinthine approach in which the cochlear nerve was preserved. In each patient, promontory stimulation elicited repeatable behavioral responses. These responses were consistent over a 9-month period of observation.

Chronic otitis media and sensorineural hearing loss: is there a clinically significant relation?

Previous investigations into the possible relation between chronic otitis media (COM) and sensorineural hearing loss (SNHL) have resulted in differing results and conclusions. A retrospective study was conducted to examine the relation between COM and SNHL, using strict selection criteria for cases so as to eliminate co-variables. In addition, various COM parameters were studied to determine if a correlation with the severity of the SNHL existed. At the University of Virginia, charts of all patients undergoing chronic ear surgery from September 1983 to March 1993 were reviewed. Sixty-nine patients met the following criteria: unilateral COM and no history of head trauma, meningitis, post-traumatic tympanic membrane perforation, labyrinthine fistula, or coexisting otologic condition of either ear. From these charts, audiograms were then analyzed for evidence of SNHL, defined as the difference in preoperative bone conduction thresholds between diseased and control (normal contralateral) ears. Mean bone conduction differences were small: -0.5 dB at 500 Hz, 0.9 dB at 1,000 Hz, 4.4 dB at 2,000 Hz, and 3.6 dB at 4,000 Hz. There were nonsignificant bone conduction threshold differences that trended toward greater SNHL with diseased mucosa and cholesteatoma at 2,000 and 4,000 Hz. There was no consistent correlation between severity of SNHL and presence of otorrhea, degree of ossicular erosion, or duration of disease. The authors conclude that COM may cause SNHL, but in the vast majority of patients this loss is not clinically significant.

Vagal body tumors.

Six cases of vagal body tumor are reviewed. All first presented as painless neck masses with normal cranial nerve function. Otologic symptoms were infrequent, occurring only with temporal bone involvement. In true vagal paragangliomas, cranial nerve and auditory function is usually preserved until there is extensive disease of the skull base. Tumor progression after radiotherapy was documented in four patients, three of whom were treated with 4500 cGy or more. One patient was found to have regional lymph node metastases. The six patients had a total of 10 head and neck paragangliomas, illustrating the high incidence of synchronous and metachronous lesions. Because of the high incidence of multiple lesions, these tumors threaten lower cranial nerves bilaterally in many instances. Because cranial nerve function is preserved until late, and because vagal and accessory nerve paralysis is usually unavoidable with resection, we advocate conservative treatment in selected cases. It may be reasonable to postpone surgery until cranial nerve impairment becomes evident or other vital structures are threatened.

Intraocular pressure as an index of ocular injury in orbital fractures.

An improved method of screening for ocular injuries in patients sustaining orbital fractures is proposed. We performed a retrospective study of 107 patients who sustained orbital fractures. Intraocular pressures were measured on presentation in 17 patients and were found to be elevated on the side of the injury in eight patients, five (63%) of whom had significant ocular injury. No patient with normal intraocular pressure was found to have an ocular injury. In a prospective study, the intraocular pressures of 30 patients sustaining orbital fractures were measured. Twelve patients (40%) had normal (less than 22 mm Hg) and bilaterally symmetric (less than 3 mm Hg difference) intraocular pressures. One (8%) of these patients sustained ocular injury. In contrast, 18 patients (60%) had either an elevated intraocular pressure (greater than 22 mm Hg) or a difference between eyes of greater than or equal to 3 mm Hg. Eleven (61%) of these patients were found to have sustained an ocular injury. We conclude that intraocular hypertension or significant interocular pressure differences should alert the physician to a potential ocular injury.

Effects of fluid shear and temperature on protein adsorption on teflon surfaces.

Partial gold decoration TEM images of protein adsorption on Teflon have been reliably obtained and confirmed by independent imaging methods. Albumin deposits are irregular in shape, unconnected, with low surface coverage in the range of 25-2500 mg/dl. The deposits tend to follow surface structural details to a scale of 4000A. In contrast, Cohn I fibrinogen deposits are reticulated, connected, with high surface coverage, which do not reflect details of surface structure, in the range of 3-300 mg/dl. The albumin adsorbates decrease with increasing wall shear rate and have negligible temperature dependence. The Cohn I fibrinogen adsorbates are not shear dependent, up to 800 sec-1, nor are they temperature dependent from 20-40 degrees C. These results support the view that nondenatured albumin maintains weak protein-polymer and protein-protein bonds, whereas Cohn I fibrinogen adsorbates are fostered by strong protein-protein interactions.