Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction.

DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineural hearing loss with vestibular pathology. Here we report three missense mutations in human COCH (previously described as Coch5b2), a novel cochlear gene, in three unrelated kindreds with DFNA9. All three residues mutated in DFNA9 are conserved in mouse and chicken Coch, and are found in a region containing four conserved cysteines with homology to a domain in factor C, a lipopolysaccharide-binding coagulation factor in Limulus polyphemus. COCH message, found at high levels in human cochlear and vestibular organs, occurs in the chicken inner ear in the regions of the auditory and vestibular nerve fibres, the neural and abneural limbs adjacent to the cochlear sensory epithelium and the stroma of the crista ampullaris of the vestibular labyrinth. These areas correspond to human inner ear structures which show histopathological findings of acidophilic ground substance in DFNA9 patients.

Behavioral inhibition and clinical outcomes in children with cochlear implants.

OBJECTIVES/HYPOTHESIS: Individual speech and language outcomes of deaf children with cochlear implants (CIs) are quite varied. Individual differences in underlying cognitive functions may explain some of this variance. The current study investigated whether behavioral inhibition skills of deaf children were related to performance on a range of audiologic outcome measures. DESIGN: Retrospective analysis of longitudinal data collected from prelingually and profoundly deaf children who used CIs. METHODS: Behavioral inhibition skills were measured using a visual response delay task that did not require hearing. Speech and language measures were obtained from behavioral tests administered at 1-year intervals of CI use. RESULTS: Female subjects showed higher response delay scores than males. Performance increased with length of CI use. Younger children showed greater improvement in performance as a function of device use than older children. No other subject variable had a significant effect on response delay score. A series of multiple regression analyses revealed several significant relations between delay task performance and open set word recognition, vocabulary, receptive language, and expressive language scores. CONCLUSIONS: The present results suggest that CI experience affects visual information processing skills of prelingually deaf children. Furthermore, the observed pattern of relations suggests that speech and language processing skills are closely related to the development of response delay skills in prelingually deaf children with CIs. These relations may reflect underlying verbal encoding skills, subvocal rehearsal skills, and verbally mediated self-regulatory skills. Clinically, visual response delay tasks may be useful in assessing behavioral and cognitive development in deaf children after implantation.

PET imaging of cochlear-implant and normal-hearing subjects listening to speech and nonspeech.

Functional neuroimaging with positron emission tomography (PET) was used to compare the brain activation patterns of normal-hearing (NH) with postlingually deaf, cochlear-implant (CI) subjects listening to speech and nonspeech signals. The speech stimuli were derived from test batteries for assessing speech-perception performance of hearing-impaired subjects with different sensory aids. Subjects were scanned while passively listening to monaural (right ear) stimuli in five conditions: Silent Baseline, Word, Sentence, Time-reversed Sentence, and Multitalker Babble. Both groups showed bilateral activation in superior and middle temporal gyri to speech and backward speech. However, group differences were observed in the Sentence compared to Silence condition. CI subjects showed more activated foci in right temporal regions, where lateralized mechanisms for prosodic (pitch) processing have been well established; NH subjects showed a focus in the left inferior frontal gyrus (Brodmann's area 47), where semantic processing has been implicated. Multitalker Babble activated auditory temporal regions in the CI group only. Whereas NH listeners probably habituated to this multitalker babble, the CI listeners may be using a perceptual strategy that emphasizes 'coarse' coding to perceive this stimulus globally as speechlike. The group differences provide the first neuroimaging evidence suggesting that postlingually deaf CI and NH subjects may engage differing perceptual processing strategies under certain speech conditions.

Electrically evoked potentials in cochlear implant subjects.

A series of experiments was performed to study electrically evoked potentials as indicators of subject response to cochlear implantation. 1. Brain stem evoked responses to electrical stimulation were compared to those obtained by acoustic stimulation in guinea pigs. The response pattern was similar and was independent of the site of placement of the stimulus electrode (cochlear base or apex) or of the extracochlear ground electrode (eustachian tube or temporalis muscle) when evoked electrically. 2. Electrically evoked middle latency responses were recorded and compared to subjective behavioral thresholds in patients who had received a single channel cochlear implant (House-Urban). The behavioral responses to the same stimuli were similar. 3. Electrically evoked auditory brain stem responses were studied in single channel cochlear implant subjects (3M/House). When evoked electrically, potential latencies were shorter and interpeak intervals narrower than acoustically evoked potentials.

Cochlear implantation in auditory neuropathy.

OBJECTIVE: Auditory neuropathy is a recently described clinical entity characterized by sensorineural hearing loss in which the auditory evoked potential (ABR) is absent but otoacoustic emissions are present. This suggests a central locus for the associated hearing loss. In this study the results observed in a child with auditory neuropathy who received a cochlear implant are presented and compared with those of a matched group of children who were recipients of implants. METHODS: A single-subject, repeated-measures design, evaluating closed-set and open-set word recognition abilities was used to assess the subject and a control group of matched children with implants who had also experienced a progressive sensorineural hearing loss. RESULTS: The subject demonstrated improvements in vowel recognition (82% correct) by 1 year after implantation, which were only slightly lower than the control group. Consonant recognition and open-set word recognition scores were significantly lower. CONCLUSION: Caution should be exercised when considering cochlear implantation in children with auditory neuropathy. As with conventional hearing aids, less than optimal results may be seen.

Cochlear implants for deaf children.

Fifteen profoundly deaf patients under the age of 18 years have received a 3M/House cochlear implant. The surgical procedure employed is essentially the same as that used in adults with a few modifications to accommodate for the smaller dimensions of the mastoid process and the thinness of the scalp and temporal squama. Pediatric subjects receive timing and intensity information at similar thresholds as adults implanted with this device which contributes to improvement in speech production to various degrees. All subject groups demonstrated significant language delays as a result of their profound hearing losses. Postimplantation, more growth was seen in receptive than in expressive language skills. However, the growth observed did not exceed that expected in profoundly deaf children as reported in the literature. Language growth as a result of the cochlear implant alone is yet to be documented in our patients.

Cochlear implantation in common cavity malformations using a transmastoid labyrinthotomy approach.

The transmastoid facial recess approach has become the standard technique for cochlear implantation. Although this approach has been used for implantation in patients with common cavity deformities, it is not without increased risk to the facial nerve. Using a direct approach to the common cavity that circumvents the facial recess, we have successfully implanted four patients with common cavity deformities. An aberrant facial nerve in one patient would have precluded placement of the electrode array using standard cochlear implant techniques. As demonstrated in these four patients, the direct approach to the common cavity is an effective approach for placement of the electrode array, minimizes risk to the facial nerve, and may decrease the likelihood of postoperative cerebrospinal fluid leaks. Intraoperative video footage demonstrates the feasibility and facility of this approach in patients with common cavity deformities.

Variables affecting implant performance in children.

This study examined the variables that contribute to the large individual differences in the speech perception skills of children with the Nucleus multichannel cochlear implant. Sixty-one children were tested on four measures of speech perception: two tests of closed-set word recognition, one test of open-set recognition of phrases, and one open-set monosyllabic word test, scored on the basis of the percentage of phonemes as well as words identified correctly. The results of a series of multiple regression analyses revealed that the variables of processor type, duration of deafness, communication mode, age at onset of deafness, length of implant use, and age implanted accounted for roughly 35% of the variance on two tests of closed-set word recognition, and 40% of the variance on measures that assessed recognition of words or phonemes in an open set. Length of implant use accounted for the most variance on all of the speech perception measures.

Electrically evoked brainstem responses in cochlear implant recipients.

Electrical stimulation of the auditory nerve in the profoundly deaf population through implanted cochlear prostheses has increased the need for reliable electrophysiologic assessment tools. We have recorded electrically evoked brainstem responses (EABRs) in 21 subjects who have received a 3M/House cochlear implant. Recordings have been made, both intraoperatively and postoperatively, in the laboratory setting. The recording technique, methods of stimulus artifact suppression, and results of our measurements are described. Clinical applications of this technology are suggested.

Congenital conductive hearing loss in Apert syndrome.

Acrocephalosyndactyly (Apert syndrome) is a rare craniosynostotic syndrome characterized by acrocephaly, syndactyly of the hands and feet, and--occasionally--conductive hearing loss. We report three cases of conductive hearing loss in Apert syndrome. One patient was found to have bilateral stapes fixation. His daughter (the second case) had chronic bilateral otitis media with effusion. The third case involved a fixed incus and hypomobile stapes. The management of these patients and a review of the literature are presented.

Preservation of hearing in neurofibromatosis 2.

Preservation of hearing in the neurofibromatosis 2 (central neurofibromatosis) patient has been infrequently documented. This goal can be attained in selected patients and should be more frequently accomplished in the future with improved diagnostic capabilities and improved surgical techniques. We report three patients in whom this elusive goal has been accomplished.

Sigmoid sinus thrombosis diagnosis by contrasted MRI scanning.

Septic thrombosis of the transverse-sigmoid sinuses and the jugular bulb is a highly lethal condition. The presenting signs and symptoms of this disease entity are subtle and not in proportion to the magnitude of the problem. Later in the disease course, sudden fulminant findings appear. A high index of suspicion, combined with scanning techniques of either enhanced MRI or CT, allows prompt diagnosis and treatment. MRI enhanced with gadolinium-DTPA (Gd) is a valuable adjunct that confirms the diagnosis and delineates the extent of suspected pathology.

Middle fossa surgery. Report of 153 cases.

The principal indications for the middle cranial fossa approach to the petrous apex and internal auditory canal are section of the vestibular nerves in vertigo, management of lesions of the labyrinthine segment of the facial nerve, and removal of mass lesions of the internal auditory canal. We report 153 cases of pathosis of the temporal bone and related structures for which this approach was used.

Long-term intracochlear implantation in man.

Whether long-term intracochlear implantation and direct electrical stimulation of the acoustic nerve will induce intracochlear bone growth or cause further degeneration of a severely compromised auditory system is an important clinical consideration. Thin-section CT evaluations of the cochleas of six subjects who have used their cochlear implant devices on a daily basis for 3 or more years demonstrated no evidence of osteoneogenesis of the cochlea in the vicinity of the active electrode. No corrosion of the electrode or insulation material was noted on electron microscopy of an explanted electrode system. Electrical threshold and dynamic range measurements have remained stable or even improved during the period of observation. Performance measures using a variety of audiologic tests and speech-tracking scores have demonstrated stability of performance.

Comparison of speech perception abilities in deaf children with hearing aids or cochlear implants.

The speech perception abilities of deaf children with a single- or multi-channel cochlear implant are compared with those of deaf children who derive substantial benefit from conventional hearing aids. The children with hearing aids have unaided pure-tone thresholds ranging from 90- to 110-dB HL through at least 2000 Hz, and aided thresholds of 30- to 60-dB HL. The group data show that the speech perception scores of the subjects with hearing aids were significantly higher than those of the subjects with implants on a range of speech perception measures. Although a few subjects with implants achieved scores as high as those who used hearing aids, the majority did not. Even though the children with implants receive substantial benefit from their devices, they continue to have limited auditory perception abilities relative to their peers who derive benefit from conventional hearing aids. The data highlight the importance of establishing hearing aid benefit in potential candidates for implant.

Contemporary management of neurofibromatosis.

The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described.

Effect of age at onset of deafness on children's speech perception abilities with a cochlear implant.

The speech perception abilities of 37 children with cochlear implants (single-channel or multichannel) were examined as a function of age at onset of deafness. There was no significant difference in the speech perception abilities of implanted children who were born deaf and those of implanted children who lost their hearing during the first 3 years of life. In contrast, the performance of children whose age at onset of deafness was 5 years or later was significantly better than that of the children with congenital or early-acquired deafness on tests of stress pattern categorization, closed-set word identification, open-set identification of common phrases, and lipreading enhancement.

Cochlear implants.

Cochlear implants are an appropriate alternative for selected deaf children and adults who do not benefit from conventional amplification. Improvements have been documented in speech perception and speech production skills. Multichannel systems, which provide spectral information in addition to temporal and intensity cues, have demonstrated performance advantages in children as they have in adults.

Cochlear implants in children.

Cochlear implants are electronic prostheses that provide a high quality sense of hearing to severely and profoundly deaf children and adults. As improvements in surgical technique and device performance have occurred, indications for implantation have expanded.

Enhancement of expressive language in prelingually deaf children with cochlear implants.

Expressive language skills were assessed in two groups of prelingually-deafened children using the Reynell Developmental Language Scales (RDLS). Results from a group of 89 unimplanted subjects provided cross-sectional data which suggested that profoundly deaf children without implants, on average, could only be expected to make 5 months of expressive language growth in one year. Twenty-three children who received cochlear implants made up the second group of subjects and were administered the RDLS at three intervals: preimplant, 6-, and 12-months postimplant. The scores obtained at the post-implant intervals were then compared to scores that would be predicted on the basis of maturation alone, without the implant (these predictions were formulated based on the data obtained from the unimplanted subjects). At the 12-month postimplant interval, the observed mean language score was significantly higher than the predicted score. Although the mean group data were extremely encouraging, wide inter- subject variability was observed. Although the implant subjects, as a group, were substantially delayed compared with their normal hearing peers, their rate of language growth was found to match that of hearing peers, following implantation. Thus, the gap between chronological age and language age, which normally widens over time in deaf children, remained constant. Preliminary analyses over the first 2.5 years post-implant are consistent with this trend. These results suggest that early implantation (before age 3) might be beneficial to profoundly deaf children because the language delays at the time of implantation would be much smaller.