H. Alexander Arts

Identification and Characterization of Choline Transporter-Like Protein 2, an Inner Ear Glycoprotein of 68 and 72 kDa That Is the Target of Antibody-Induced Hearing Loss

The Kresge Hearing Research Institute-3 (KHRI-3) antibody binds to a guinea pig inner ear supporting cell antigen (IESCA) and causes hearing loss. To gain insight into the mechanism of antibody-induced hearing loss, we used antibody immunoaffinity purification to isolate the IESCA, which was then sequenced by mass spectroscopy, revealing 10 guinea pig peptides identical to sequences in human choline transporter-like protein 2 (CTL2). Full-length CTL2 cDNA sequenced from guinea pig inner ear has 85.9% identity with the human cDNA. Consistent with its expression on the surface of supporting cells in the inner ear, CTL2 contains 10 predicted membrane-spanning regions with multiple N-glycosylation sites. The 68 and 72 kDa molecular forms of inner ear CTL2 are distinguished by sialic acid modification of the carbohydrate. The KHRI-3 antibody binds to an N-linked carbohydrate on CTL2 and presumably damages the organ of Corti by blocking the transporter function of this molecule. CTL2 mRNA and protein are abundantly expressed in human inner ear. Sera from patients with autoimmune hearing loss bind to guinea pig inner ear with the same pattern as CTL2 antibodies. Thus, CTL2 is a possible target of autoimmune hearing loss in humans.

Familial Large Vestibular Aqueduct Syndrome

The large vestibular aqueduct syndrome (LVAS) is a distinct clinical entity characterized by stepwise progressive sensorineural hearing loss associated with isolated enlargement of the vestibular aqueduct.

Hearing preservation and facial nerve outcomes in vestibular schwannoma surgery: results using the middle cranial fossa approach.

Objective: To evaluate surgical results using the middle cranial fossa approach for hearing preservation vestibular schwannoma surgery. Study Design: Retrospective case review. Setting: Tertiary referral academic center. Patients: Seventy-three consecutive patients with vestibular schwannoma operated on using the middle cranial fossa approach between February 1999 and February 2005. Interventions: The tumors were removed via the middle cranial fossa approach with modifications to improve exposure. Standard auditory brainstem and facial nerve monitoring were used. Main Outcome Measures: Pre- and postoperative hearing measures and facial function, tumor size, and postoperative complications. Hearing status was categorized into Classes A, B, C, and D as described by the American Academy of Otolaryngology-Head and Heck Surgery “Guidelines for the Evaluation of Hearing Preservation in Acoustic Neuroma, 1995.” Results: Thirty-four patients presented with Class A hearing preoperatively. Among patients presenting with Class A hearing, a total of 27 (80%) maintained Class A or B hearing postoperatively. Of these, 21 (62%) remained in Class A, 6 (18%) deteriorated slightly to Class B, and 7 (20%) deteriorated to Class D postoperatively. Twenty-eight patients presented with Class B hearing preoperatively. Of these, 18 (64%) remained in Class B, 3 (11%) deteriorated to Class C, and 7 (25%) deteriorated to Class D. Three patients had Class C hearing preoperatively. Of these, 2 (66%) remained in Class C and 1 (33%) deteriorated to Class D. Eight patients presented in Class D and one of these improved to Class C postoperatively. Overall, 62 patients presented with useful (Class A or B) hearing and 45 (73%) remained in Class A or B. Nineteen patients had tumors larger than 10 mm in greatest dimension and had Class A or B hearing preoperatively. Of these, 11 (58%) retained Class A or B hearing postoperatively. At 4 months or greater follow-up, facial nerve outcome were excellent in 96%: House-Brackmann Grade I in 61 (85%), Grade II in 8 (11%), and Grade III in 3 (4%). There were no Grade IV, V, or VI results on final follow-up. Six (8%) patients developed cerebrospinal fluid leaks. Conclusion: By achieving excellent exposure and using meticulous microsurgical technique, it is possible to resect small vestibular schwannomas via the middle fossa approach, with preservation of hearing at excellent or preoperative levels in the majority of patients, with excellent or satisfactory facial nerve outcomes in 96% of patients.

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.

Cochlear implantation in chronic suppurative otitis media

Objective To evaluate management options for cochlear implantation in patients with chronic suppurative otitis media. Study Design Retrospective case review. Setting Tertiary referral center with a large cochlear implant program. Patients Ten patients with chronic suppurative otitis media who received cochlear implants were identified. Case history, etiology of hearing loss, and management of the ear with the implant were evaluated. Interventions Cochlear implantation and subsequent rehabilitation. Main Outcome Measures Early and late complications were evaluated. Results No early or late complications were identified in this group of patients after an average follow-up period of about 4 years. Conclusion Cochlear implantation can be safely achieved in patients with chronic suppurative otitis media. There are several options for the management of these patients, and the approach chosen should be individualized on the basis of clinical findings.

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.

External auditory canal closure in cochlear implant surgery.

Objective To evaluate surgical techniques and complications associated with external auditory canal (EAC) closure in cochlear implant surgery. Study Design Retrospective case review. Setting Tertiary referral center with a large cochlear implant program. Patients Twenty-eight patients (8 adults and 20 children) underwent multichannel cochlear implantation with EAC closure. The follow-up periods ranged between 1 and 10 years. Closure of the EAC was performed in conjunction with implantation of ears with chronic suppurative otitis media or cochlear drill-out procedures for ossification, or for access to the cochlea in patients with abnormal temporal bone anatomy. A modified Rambo technique was used for EAC closure in all but one case. Interventions Cochlear implantation with EAC closure and subsequent clinical and radiologic follow-up. Main Outcome Measures Postoperative complications or the development of cholesteatoma in the implanted ear. Results Cholesteatoma developed in the implanted ear in two patients. Breakdown of EAC closure occurred in one of these patients. The details of these patients are reviewed. Conclusion Closure of EAC can be done with relatively low risk. Close and careful follow-up is required for early detection of a developing cholesteatoma.

Reversible electrocochleographic abnormalities in superior canal dehiscence.

Objective: Electrocochleography (ECoG) is often used in the evaluation of episodic vertigo, and abnormal findings are commonly thought to be due to endolymphatic hydrops. We have observed that a number of patients with abnormal ECoG were ultimately found to have superior semicircular canal dehiscence (SSCD). Therefore, we examined the electrocochleographic findings in a series of patients with documented SSCD. Study Design: Retrospective case series. Setting: Academic medical center. Patients: Seven adult patients with unilateral SSCD and 4 patients with bilateral SSCD who underwent tympanic ECoG as part of a diagnostic or preoperative evaluation that also included vestibular-evoked myogenic potentials (VEMPs). Interventions: Patients underwent audiometric testing, ECoG, VEMP, and high-resolution temporal bone computed tomography reformatted to optimally view the superior semicircular canal. Five patients underwent superior canal obliteration. Postoperative VEMP and ECoG were performed in 4 of these patients. Intraoperative continuous ECoG was performed in 1 patient. Main Outcome Measures: Summating potential to action potential (SP/AP) ratio on ECoG. Results: Fourteen of 15 ears confirmed to have SSCD on computed tomographic imaging were found to have an elevated SP/AP ratio (defined as >0.40). In one patient with bilateral SSCD, the ear with the radiographically less severe dehiscence had an SP/AP ratio of 0.40, at the upper limit of normal, and a normal VEMP threshold. In all 4 patients who underwent obliteration of the dehiscent canal, and for whom postoperative test results were available, the SP/AP ratio normalized in the operated ear. In the 1 patient who underwent intraoperative ECoG, the SP/AP ratio normalized immediately after canal occlusion. Conclusion: An elevated SP/AP ratio seems to be a consistent finding in SSCD syndrome and, like the other abnormal audiometric and electrophysiologic findings associated with the syndrome, normalizes after surgical correction. Elevation of the SP/AP ratio has historically been associated with endolymphatic hydrops. The present findings expand the differential diagnosis of an abnormal ECoG and may shed light on the origin of an elevated summating potential.

Role of electrically evoked auditory brainstem response in cochlear implantation of children with inner ear malformations.

Objective: To evaluate the usefulness of promontory electric auditory brainstem response (EABR) testing in children with inner ear malformations before cochlear implantation indicated by postoperative speech performance. Study Design: Retrospective analysis. Setting: Tertiary academic cochlear implant center. Patients: Forty-three children with congenital inner ear malformations, of which 39 received a cochlear implant. Age at implant ranged from 12 months to 13 years. Patients were categorized into 3 groups based on the type of malformations. Groups 1 and 2 involved malformations of the cochlea and/or vestibular organ. Group 3 consisted of children with narrow internal auditory canal. Interventions: Preoperative EABR testing with threshold, Wave V amplitude, and latency determination. Main Outcome Measures: Postoperative speech perception performance was measured using Glendonald Auditory Speech Perception Tests for words and sentences, Northwestern University-Childrens Perception of Speech test, and minimal pairs test. Patients were further categorized into a speech perception category based on these test results. Results: Mean values for EABR threshold, Wave V amplitude, and latency for Group 1 (11 patients) were 485 &mgr;A, 0.21 &mgr;V, and 4.51 milliseconds, respectively. Mean values for Group 2 (20 patients) were 556 &mgr;A, 0.26 &mgr;V, and 4.45 milliseconds, respectively. Mean values for Group 3 (8 patients) were 500 &mgr;A, 0.11 &mgr;V, and 4.65 milliseconds, respectively. Open-set sentence recognition was possible in 73% in Group 1, 30% in Group 2, and 38% in Group 3 by 36 months after implant activation. Patients with lower preoperative EABR threshold (<600 &mgr;A) had better postoperative speech performance (p < 0.05). Larger Wave V amplitude and shorter latency were associated with better speech performance. Conclusion: Preoperative EABR is useful in determining cochlear implant candidacy in children with inner ear malformations. Results of this study indicate that the EABR accurately predicts outcome when cochlear implant efficacy is uncertain.

Durability of hearing preservation after microsurgical treatment of vestibular schwannoma using the middle cranial fossa approach: Clinical article

OBJECT The middle cranial fossa (MCF) approach is a microsurgical technique described as a primary option in the treatment of small, intracanalicular schwannomas involving the eighth cranial nerve. Excellent rates of complete tumor resection, hearing preservation, preservation of facial nerve function, and low complication rates have been reproduced using this technique. However, the durability of hearing preservation attained using the various treatment options has not been adequately assessed. The purpose of this study was to evaluate the durability of long-term hearing preservation in patients with vestibular schwannoma (VS) treated via the MCF approach. The authors hypothesize that hearing preservation in these patients will prove to be durable years after treatment in a high percentage of cases. METHODS Retrospective medical chart review was performed in 103 consecutive patients undergoing resection of VS via a modified MCF approach between 1999 and 2008. Patients in whom surgical goals were gross-total resection and hearing preservation were included. Preoperative and postoperative hearing assessment was performed using standard audiometric testing, and classified according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines as a primary outcome measure. Outcomes and neurological complications initially, and at 1, 3, and 5 years following operation were analyzed. RESULTS Initial hearing preservation rates were in keeping with the best previously published results. At initial postoperative audiometric follow-up, of the patients presenting with Class A hearing, 67% remained Class A, 17% were Class B, 1% were Class C, and 15% were Class D. Of patients presenting with Class B hearing, 24% were Class A, 53% remained Class B, 6% were Class C, and 18% were Class D. Of patients presenting with Class C hearing, 100% remained Class C. To assess the durability of hearing preservation in our patients, the authors evaluated hearing function at regular intervals after the initial postoperative audiometric follow-up. Audiometric data were available for 56 patients at 5-year follow-up. Of the 20 patients with Class A hearing at initial postoperative follow-up with 5-year follow-up, 13 (65%) remained Class A, 6 (30%) were Class B, and 1 (5%) was Class C. Of the 12 patients with Class B hearing at initial postoperative follow-up with 5-year follow-up, 4 (33%) were Class A, 4 (33%) remained Class B, and 4 (33%) were Class C. Of the 3 patients with Class C hearing at initial postoperative follow-up with 5-year follow-up, all 3 (100%) remained Class C. CONCLUSIONS A majority of patients with preserved hearing following the MCF approach for treatment of VS experience durability of their preserved hearing at 5-year follow-up. The initial AAO-HNS classification was preserved in 13 (65%) of the 20 patients who had Class A hearing at 5 years, and in 8 (67%) of the 12 who had Class B hearing at 5 years. Overall, a decline in AAO-HNS classification was noted in 15% of patients with preserved Class A hearing, and in 33% of those with preserved Class B hearing. Facial nerve function was preserved in 91% of cases. Superior hearing preservation as well as good outcomes in facial nerve function and few serious complications can be accomplished using the MCF approach for resection of small VSs.