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.

Effects of trigeminal ganglion stimulation on unit activity of ventral cochlear nucleus neurons.

The trigeminal ganglion sends a projection to the granule and magnocellular regions of the ventral cochlear nucleus (VCN; [J Comp Neurol 419 (2000) 271]), as well as to the cochlea ([Neuroscience 79 (1997) 605; Neuroscience 84 (1998a) 559]). We investigated the effects of electrically stimulating the trigeminal ganglion on unit responses in the guinea-pig VCN. Responses consisted of one, two or more phases of excitation, sometimes followed by a longer inhibitory phase. The latencies to the first excitation peak ranged between 5 and 17 ms from the onset of stimulation. These responses were preceded by a slow wave potential evoked by the stimulation. Applying kainic acid, which eliminates VIIIth nerve responses, diminished the firing rates of VCN units to trigeminal stimulation, and increased their first spike latencies. Cochlear destruction had a similar effect. The responses in VCN evoked by trigeminal ganglion stimulation therefore appear to result from direct stimulation of the trigeminal ganglion-cochlear nucleus pathway, as well as modulation by the trigeminal ganglion-cochlear pathway. Alternatively, a reduction in spontaneous rate of VCN neurons by removal of VIIIth nerve input could explain the decreased response to trigeminal stimulation after cochlear manipulations. The modulation of firing rate in second order auditory neurons by first order somatosensory neurons could influence central auditory targets and may be involved in generating or modulating perceptions of phantom sounds which can be modified by manipulations of somatic regions of the head and neck ("somatic tinnitus").

Selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization.

OBJECTIVE: To determine if selective reinnervation of the cricothyroid muscle could be achieved with muscle-nerve-muscle neurotization. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Three consecutive patients with high vagal lesions that resulted in unilateral laryngeal paralysis. INTERVENTIONS: Patients underwent laryngeal reinnervation with ansa hypoglossi to recurrent laryngeal nerve anastomosis. In addition, patients underwent selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization technique. MAIN OUTCOME MEASURES: Objective and subjective improvement in voice quality and electromyographic evidence of selective reinnervation of the cricothyroid muscle. RESULTS: All patients recovered normal or near-normal speaking voice and had normal objective measures of voice quality. They also showed electromyographic evidence of cricothyroid muscle reinnervation. CONCLUSION: The muscle-nerve-muscle neurotization technique was successful in providing selective reinnervation of the cricothyroid muscle in our 3 patients.

Multichannel cochlear implantation in visually impaired patients.

OBJECTIVE: To evaluate the outcome of cochlear implantation in patients with severe to profound hearing loss and visual impairment. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center with a large cochlear implant program. PATIENTS: Six adults and two children with severe or profound hearing loss and significant visual impairment underwent multichannel cochlear implantation. Follow-up period ranged from 6 months to 9 years. Case history, etiology of visual and hearing loss, and benefit from cochlear implant were evaluated. INTERVENTIONS: Cochlear implantation and subsequent rehabilitation. MAIN OUTCOME MEASURES: Speech perception measures were selected based on the patient age and cognitive abilities. Identical measures were used in each patient before and after implantation. RESULTS: As a group, patients did well after cochlear implantation. There was significant improvement in speech perception when compared with the score before implantation. CONCLUSIONS: Cochlear implants can play a significant rehabilitative role in patients with severe visual and auditory impairment. Additional skills are required by the implant team for rehabilitation of patients with multiple sensory deficits.

Auditory brain stem response in small acoustic neuromas.

OBJECTIVE: The auditory brain stem response (ABR) has been criticized recently as an insensitive measure for the detection of small acoustic neuroma (AN). This study was undertaken to evaluate our experience with the efficacy of ABR in detection of small tumors. STUDY DESIGN: Retrospective case review. Twenty-five patients with surgically proven small ANs measuring 1 cm or less were reviewed. In addition, 568 patients who underwent screening ABR were reviewed to evaluate the rate of false positive results at our institution. RESULTS: ABR was abnormal in 92% of patients with small AN in this series. Screening ABR was abnormal in approximately 19% of cases, one-third of which were found to have AN on magnetic resonance imaging testing. CONCLUSION: With strict adherence to optimal technique and evaluation criteria, the ABR remains a viable option for AN screening, especially in elderly patients or when there is a low index of suspicion.

Diagnosis and initiating treatment for peripheral system disorders: imbalance and dizziness with normal hearing.

Disorders affecting the peripheral vestibular system commonly involve the peripheral auditory system causing hearing loss. There are a number of disorders, however, that selectively involve the peripheral vestibular system causing dizziness without hearing loss. These disorders include benign paroxysmal positional vertigo, vestibular neuritis, recurrent vestibulopathy, familial vestibulopathy, and bilateral idiopathic vestibulopathy. This article reviews these disorders and their diagnosis and management.

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.

Multichannel cochlear nucleus stimulation.

Stimulation of the cochlear nucleus (CN) has been used on a limited basis for rehabilitation of a select group of patients with bilateral acoustic neuromas. These patients were implanted with an electrode placed on the surface of the CN after resection of their tumors. Animal studies have demonstrated greater efficiency of a penetrating CN electrode in activating the central auditory system than a surface electrode. The objective of this work was to study the electrically evoked middle latency response generated by stimulation through a penetrating multichannel CN electrode in an animal model. Six pigmented guinea pigs underwent implantation with a penetrating multichannel CN electrode. Threshold, latency, and input-output functions of electrically evoked middle latency responses with different stimulation pads were studied. There were systematic differences in the latency and amplitude of the input-output functions depending on the site of stimulation within the CN. The results support the hypothesis that discrete activation of neuronal subpopulations within the CN is possible with a penetrating multichannel microelectrode.

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.

Evaluation of clinical measures of equilibrium.

OBJECTIVE: Evaluate the clinical utility of several simple measures of static and dynamic equilibrium in human subjects. In particular, one proposed clinical measure, the Clinical Test of Sensory Integration and Balance (CTSIB) was compared with dynamic posturography for the measurement of postural control capabilities. STUDY DESIGN: Cross-sectional study of normal subjects and prospective observational study of the same performance measures in vestibular disorder patients. SETTING: Academic tertiary care referral center. PARTICIPANTS: Data were collected for all test measures from a group of normal subjects (ages, 20 to 79 years), as well as for a group of patients undergoing treatment for vestibular dysfunction. RESULTS: Data suggest that several semiquantitative clinical tests of static and dynamic equilibrium can be helpful in evaluating and monitoring patients with chronic vestibular dysfunction. The CTSIB results seem to correlate well with dynamic posturography, suggesting that this measure may be useful in identifying patients with abnormal postural control. Formal dynamic posturography testing appears to be more sensitive in detecting abnormal postural control and more exact in defining the specific pattern of dysfunction. CONCLUSION: Simple clinical measures of static and dynamic equilibrium can reliably distinguish vestibular disorder patients from normal subjects. Dynamic posturography continues to play an important role in the functional evaluation and management of vestibular disorder patients.

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.

Metabolic activity of the central auditory structures following prolonged deafferentation.

The goal of this work was to evaluate, using autoradiographic techniques, the effects of variable periods of deafness on resting and evoked metabolic activity in central auditory structures elicited by direct electrical cochlear nucleus (CN) stimulation. Thirty-five pigmented guinea pigs, divided into five groups, underwent acute implantation of bipolar electrodes in the CN. One group was not deafened and served as hearing controls. The other four groups were deafened using an established protocol of sequential kanamycin/ethacrynic acid treatment and were tested at 4 weeks, 9 weeks, 16 weeks, and 15 months after deafening. Threshold currents for eliciting evoked middle latency responses (EMLRs) with direct CN stimulation were not significantly different between hearing and deafened groups. Autoradiographic data showed progressive reduction of the evoked metabolic response with incremental periods of deafferentation. Nevertheless, central auditory structures remained responsive to direct electrical stimulation of the CN. These data indicate that direct CN stimulation remains capable of activating the auditory tract despite prolonged periods of deafness.

Direct electrical stimulation of the cochlear nucleus: surface vs. penetrating stimulation.

Prosthetic stimulation of the cochlear nucleus (CN) has been used for rehabilitation of profoundly deaf patients who are not suitable candidates for cochlear implants. The goal of this article was to assess the relative effectiveness of surface vs. penetrating stimulation of the CN. Electrophysiologic and autoradiographic measures were used to study central auditory system activation elicited by direct stimulation of the CN. Eighteen pigmented guinea pigs, divided into three groups, underwent acute implantation of bipolar electrodes in the CN. One group was not stimulated and acted as a control (n = 7). Electrodes were placed on the surface of the CN in one test group (n = 4) and within the CN in a second test group (n = 7). Thresholds for electrically evoked middle latency responses (EMLR) were determined and input/output (I/O) functions were obtained. The two test groups were then pulsed with [14C]-2-Deoxyglucose (2-DG) intramuscularly and stimulated for 1 hour with biphasic; charge-balanced pulses having a total duration of 400 microseconds, a repetition rate of 100/sec, and an amplitude of 200 microA. After stimulation, animals were killed and brains were harvested and prepared for autoradiography using standard techniques. Threshold current for EMLRs in the surface-stimulated group had a mean of 67.5 +/- 23.9 microA (range, 40 to 100 microA). Thresholds for in-depth stimulated group had a mean of 11.4 +/- 3.5 microA (range, 10 to 20 microA). The saturation level of the I/O function for the surface-stimulated group had a mean of 287.5 +/- 41.5 microA (range, 250 to 350 microA). The saturation level for the in-depth stimulated group had a mean of 192.9 +/- 49.5 mciroA (range, 100 to 250 microA). The dynamic range for the surface electrodes had a mean of 13.1 +/- 2.7 dB (range, 9.9 to 15.9 dB), whereas the dynamic range for the penetrating electrodes had a mean of 24.5 +/- 2.6 dB (range, 20 to 28.0 dB). Autoradiographs generated by CNS tissue from stimulated animals demonstrated no significant difference in metabolic activity of the CN between surface and in-depth stimulated groups. However, there were highly significant differences in 2-DG uptake in the contralateral superior olivary complex, contralateral inferior colliculus, and ipsilateral and contralateral lateral lemniscus, with greater uptake in in-depth stimulated preparations. Electrophysiologic and autoradiographic data suggest that a penetrating CN prosthesis is capable of activating the auditory tract at a lower threshold, with a relatively wider dynamic range than a surface prosthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Retrolabyrinthine vestibular nerve section: efficacy in disorders other than Menière's disease.

The retrolabyrinthine vestibular nerve section has evolved as an effective treatment for intractable vertigo of peripheral vestibular origin when hearing preservation is desired. This report studies the efficacy of retrolabyrinthine vestibular nerve section for control of vertigo due to causes other than Meniere's disease. This report details our experience with 42 patients with a wide variety of diagnoses. The reduced success rate of retrolabyrinthine vestibular nerve section in these patients is difficult to evaluate, as very few patients have been analyzed with respect to their specific diagnoses. Of patients who underwent retrolabyrinthine vestibular nerve section for control of vertigo, 23 patients had uncompensated vestibular neuritis and 19 others had a wide range of other diagnoses. For patients with uncompensated vestibular neuritis (n = 23), the physician record noted that 39% of patients were cured and 30% improved. This compares to our series of patients with Meniere's disease (n = 48), where 94% were cured and 2% improved. The true vestibular abnormality may be less reliably identified in patients with uncompensated vestibular neuritis, contributing to the less effective results. Since the development of a vestibular rehabilitation program, retrolabyrinthine vestibular nerve section for uncompensated vestibular neuritis has been all but abandoned. Retrolabyrinthine vestibular nerve section appears to achieve a high cure rate in patients with sensorineural hearing loss associated with their vestibular abnormalities. While retrolabyrinthine vestibular nerve section is helpful for control of vertigo in some diagnoses, a substantial incidence of persistent postoperative dysequilibrium was noted.