Cochlear implantation updates: the Dallas Cochlear Implant Program.

This report provides an overview of many research projects conducted by the Dallas Cochlear Implant Program, a joint enterprise between the University of Texas at Dallas, the University of Texas Southwestern Medical Center, and Children's Medical Center. The studies extend our knowledge of factors influencing communication outcomes in users of cochlear implants. Multiple designs and statistical techniques are used in the studies described including both cross sectional and longitudinal analyses. Sample sizes vary across the studies, and many of the samples represent large populations of children from North America. Multiple statistical techniques are used by the team to analyze outcomes. The team has provided critical information regarding electrode placement, signal processing, and communication outcomes in users of cochlear implants.

Usher syndrome IIIA gene clarin-1 is essential for hair cell function and associated neural activation.

Usher syndrome 3A (USH3A) is an autosomal recessive disorder characterized by progressive loss of hearing and vision due to mutation in the clarin-1 (CLRN1) gene. Lack of an animal model has hindered our ability to understand the function of CLRN1 and the pathophysiology associated with USH3A. Here we report for the first time a mouse model for ear disease in USH3A. Detailed evaluation of inner ear phenotype in the Clrn1 knockout mouse (Clrn1(-/-)) coupled with expression pattern of Clrn1 in the inner ear are presented here. Clrn1 was expressed as early as embryonic day 16.5 in the auditory and vestibular hair cells and associated ganglionic neurons, with its expression being higher in outer hair cells (OHCs) than inner hair cells. Clrn1(-/-) mice showed early onset hearing loss that rapidly progressed to severe levels. Two to three weeks after birth (P14-P21), Clrn1(-/-) mice showed elevated auditory-evoked brainstem response (ABR) thresholds and prolonged peak and interpeak latencies. By P21, approximately 70% of Clrn1(-/-) mice had no detectable ABR and by P30 these mice were deaf. Distortion product otoacoustic emissions were not recordable from Clrn1(-/-) mice. Vestibular function in Clrn1(-/-) mice mirrored the cochlear phenotype, although it deteriorated more gradually than cochlear function. Disorganization of OHC stereocilia was seen as early as P2 and by P21 OHC loss was observed. In sum, hair cell dysfunction and prolonged peak latencies in vestibular and cochlear evoked potentials in Clrn1(-/-) mice strongly indicate that Clrn1 is necessary for hair cell function and associated neural activation.

A mouse model with postnatal endolymphatic hydrops and hearing loss.

Endolymphatic hydrops (ELH), hearing loss and neuronal degeneration occur together in a variety of clinically significant disorders, including Meniere's disease (MD). However, the sequence of these pathological changes and their relationship to each other are not well understood. In this regard, an animal model that spontaneously develops these features postnatally would be useful for research purposes. A search for such a model led us to the Phex Hyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (Phex Hyp-Duk/Y) was previously reported to exhibit various abnormalities during adulthood, including thickening of bone, ELH and hearing loss. The reported inner-ear phenotype was suggestive of progressive pathology and spontaneous development of ELH postnatally, but not conclusive. The main focuses of this report are to further characterize the inner ear phenotype in Phex Hyp-Duk/Y mice and to test the hypotheses that (a) the Phex Hyp-Duk/Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the Phex Hyp-Duk/Y mouse is associated with obstruction of the endolymphatic duct (ED) due to thickening of the surrounding bone. Auditory brainstem response (ABR) recordings at various times points and histological analysis of representative temporal bones reveal that Phex Hyp-Duk/Y mice typically develop adult onset, asymmetric, progressive hearing loss closely followed by the onset of ELH. ABR and histological data show that functional degeneration precedes structural degeneration. The major degenerative correlate of hearing loss and ELH in the mutants is the primary loss of spiral ganglion cells. Further, Phex Hyp-Duk/Y mice develop ELH without evidence of ED obstruction, supporting the idea that ELH can be induced by a mechanism other than the blockade of longitudinal flow of endolymphatic fluid, and occlusion of ED is not a prerequisite for the development of ELH in patients.

Cochlear implant electrode insertion: the round window revisited.

OBJECTIVE: To examine aspects of round window (RW) anatomy that are relevant to its use as a portal for atraumatic insertion of cochlear implant electrodes. STUDY DESIGN: Anatomic study using human cadaveric temporal bones. METHODS: A series of 30 temporal bones was dissected to permit microscopic study of the RW region. RESULTS: The bony overhangs of the RW niche limit visibility of the RW membrane during surgery. Measurements of RW membrane area visible through a facial recess opening before and after drilling the overhangs in 15 temporal bones showed that RW membrane visibility is typically increased by a factor of 1.5 to 3 times after drilling and by as much as 13 times when the opening of the RW niche is relatively small. Observations from within the scala tympani in 15 cochlear dissections showed substantial variability in size of the RW opening available for electrode insertion. Area measurements of the portion of the RW covered by the vertical segment of the RW membrane ranged from 0.8 to 1.75 mm2 in these specimens. In addition, irregularities in contour of the RW margin may make insertion challenging, which may necessitate drilling the anterior-inferior margin of the RW. Drilling in this region should be approached with care because of the close proximity of the cochlear aqueduct opening. CONCLUSION: RW insertion can be performed in a manner that is potentially less traumatic than the standard cochleostomy insertion. It may therefore be advantageous in cases in which hearing preservation is the goal.

Progression of inner ear pathology in Ames waltzer mice and the role of protocadherin 15 in hair cell development.

The Ames waltzer (av) mouse mutant exhibits auditory and vestibular abnormalities resulting from mutation of protocadherin 15 (Pcdh15). Ames waltzer has been identified as an animal model for inner ear pathology associated with Usher syndrome type 1F. Studies correlating anatomical phenotype with severity of genetic defect in various av alleles are providing better understanding of the role played by Pcdh15 in inner ear development and of sensorineural abnormalities associated with alterations in Pcdh15 protein structure as a result of gene mutation. In this work we present new findings on inner ear pathology in four alleles of av mice with differing mutations of Pcdh15 as well as varying alterations in inner ear morphology. Two alleles with in-frame deletion mutations (Pcdh15 (av-J) and Pcdh15 (av-2J)) and two presumptive functional null alleles (Pcdh15 (av-3J) and Pcdh15 (av-Tg)) were studied. Light and electron microscopic observations demonstrated that the severity of cochlear and vestibular pathology in these animals correlates positively with the extent of mutation in Pcdh15 from embryonic day 18 (E18) up to 12 months. Electron microscopic analysis of immature ears indicated early abnormalities in the arrangement of stereocilia and the inner and outer hair cell cuticular plates, stereocilia rootlets, and the actin meshwork within the cuticular plate. In severe cases, displacement of the kinocilium and alterations in the shape of the cuticular plate was also observed. Mice harboring in-frame deletion mutations showed less disorganization of stereocilia and cuticular plates in the organ of Corti than the presumptive functional null alleles at P0-P10. A slower progression of pathology was also seen via light microscopy in older animals with in-frame deletions, compared to the presumptive functional null mutations. In summary, our results demonstrate that mutation in Pcdh15 affects the initial formation of stereocilia bundles with associated changes in the actin meshwork within the cuticular plate; these effects are more pronounced in the presumed null mutation compared to mutations that only affect the extracellular domain. The positive correlation of severity of effects with extent of mutation can be seen well into adulthood.

Gene expression analysis of distinct populations of cells isolated from mouse and human inner ear FFPE tissue using laser capture microdissection--a technical report based on preliminary findings.

Laser Capture Microdissection (LCM) allows microscopic procurement of specific cell types from tissue sections that can then be used for gene expression analysis. We first tested this method with sections of adult mouse inner ears and subsequently applied it to human inner ear sections. The morphology of the various cell types within the inner ear is well preserved in formalin fixed paraffin embedded (FFPE) sections, making it easier to identify cell types and their boundaries. Recovery of good quality RNA from FFPE sections can be challenging, however, recent studies in cancer research demonstrated that it is possible to carry out gene expression analysis of FFPE material. Thus, a method developed using mouse FFPE tissue can be applied to human archival temporal bones. This is important because the majority of human temporal bone banks have specimens preserved in formalin and a technique for retrospective analysis of human archival ear tissue is needed. We used mouse FFPE inner ear sections to procure distinct populations of cells from the various functional domains (organ of Corti, spiral ganglion, etc.) by LCM. RNA was extracted from captured cells, amplified, and assessed for quality. Expression of selected genes was tested by RT-PCR. In addition to housekeeping genes, we were able to detect cell type specific markers, such as Myosin 7a, p27(kip1) and neurofilament gene transcripts that confirmed the likely composition of cells in the sample. We also tested the method described above on FFPE sections from human crista ampullaris. These sections were approximately a year old. Populations of cells from the epithelium and stroma were collected and analyzed independently for gene expression. The method described here has potential use in many areas of hearing research. For example, following exposure to noise, ototoxic drugs or age, it would be highly desirable to analyze gene expression profiles of selected populations of cells within the organ of Corti or spiral ganglion cells rather than a mixed population of cells from whole inner ear tissue. Also, this method can be applied for analysis of human archival ear tissue.

Multichannel cochlear implant for selective neuronal activation and chronic use in the free-moving Mongolian gerbil.

BACKGROUND: Animal models for chronic multichannel cochlear implant stimulation and selective neuronal activation contribute to a better understanding of auditory signal processing and central neural plasticity. NEW METHOD: This paper describes the design and surgical implantation of a multichannel cochlear implant (CI) system for chronic use in the free-moving gerbil. For chronic stimulation, adult-deafened gerbils were connected to a multichannel commutator that allowed low resistance cable rotation and stable electric connectivity to the current source. RESULTS: Despite the small scale of the gerbil cochlea and auditory brain regions, final electrophysiological mapping experiments revealed selective and tonotopically organized neuronal activation in the auditory cortex. Contact impedances and electrically evoked auditory brainstem responses were stable over several weeks demonstrating the long-term integrity of the implant and the efficacy of the stimulation. COMPARISON WITH EXISTING METHODS: Most animal models on multichannel signal processing and stimulation-induced plasticity are limited to larger animals such as ferrets, cats and primates. Multichannel CI stimulation in the free-moving rodent and evidence for selective neuronal activation in gerbil auditory cortex have not been previously reported. CONCLUSIONS: Overall, our results show that the gerbil is a robust rodent model for selective and tonotopically organized multichannel CI stimulation. We anticipate that this model provides a useful tool to develop and test both passive stimulation and behavioral training strategies for plastic reorganization and restoration of degraded unilateral and bilateral central auditory signal processing in the hearing impaired and deaf central auditory system.

Characterization of vestibular dysfunction in the mouse model for Usher syndrome 1F.

The deaf-circling Ames waltzer (av) mouse harbors a mutation in the protocadherin 15 (Pcdh15) gene and is a model for inner ear defects associated with Usher syndrome type 1F. Earlier studies showed altered cochlear hair cell morphology in young av mice. In contrast, no structural abnormality consistent with significant vestibular dysfunction in young av mice was observed. Light and scanning electron microscopic studies showed that vestibular hair cells from presumptive null alleles Pcdh15(av-Tg) and Pcdh15(av-3J) are morphologically similar to vestibular sensory cells from control littermates, suggesting that the observed phenotype in these alleles might be a result of a central, rather than peripheral, defect. In the present study, a combination of physiologic and anatomic methods was used to more thoroughly investigate the source of vestibular dysfunction in Ames waltzer mice. Analysis of vestibular evoked potentials and angular vestibulo-ocular reflexes revealed a lack of physiologic response to linear and angular acceleratory stimuli in Pcdh15 mutant mice. Optokinetic reflex function was diminished but still present in the mutant animals, suggesting that the defect is primarily peripheral in nature. These findings indicate that the mutation in Pcdh15 results in either a functional abnormality in the vestibular receptor organs or that the defects are limited to the vestibular nerve. AM1-43 dye uptake has been shown to correlate with normal transduction function in hair cells. Dye uptake was found to be dramatically reduced in Pcdh15 mutants compared to control littermates, suggesting that the mutation affects hair cell function, although structural abnormalities consistent with significant vestibular dysfunction are not apparent by light and scanning electron microscopy in the vestibular neuroepithelia of young animals.

Characterization of a new allele of Ames waltzer generated by ENU mutagenesis.

Mutation in the protocadherin 15 (Pcdh15) gene causes hair cell dysfunction and is associated with abnormal stereocilia development. We have characterized the first allele (Pcdh15(av-nmf19)) of Ames waltzer (av) obtained by N-ethyl-N-nitrosourea (ENU) mutagenesis. Pcdh15(av-nmf19) was generated in the Neuroscience Mutagenesis Facility (NMF) at The Jackson Lab (Bar Habor, USA). Pcdh15(av-nmf19) mutants display circling and abnormal swimming behavior along with lack of auditory-evoked brainstem response at the highest intensities tested. Mutation analysis shows base substitution (A--> G) in the consensus splice donor sequence linked to exon 14 resulting in the skipping of exon 14 and the splicing of exon 13-15. This results in the introduction of a stop codon in the coding sequence of exon 15 due to shift in the reading frame. The effect of nmf19 mutation is expected to be severe since the expressed Pcdh15 protein is predicted to truncate in the 5th cadherin domain. Abnormalities of cochlear hair cell stereocilia are apparent in Pcdh15(av-nmf19) mutants near the time of birth and by about P15 (15 days after birth) there is evidence of sensory cell degeneration. Disorganization of outer hair cell stereocilia is observed as early as P2. Inner hair cell stereocilia are also affected, but less severely than those of the outer hair cells. These results are consistent with characteristics of the mutation in the Pcdh15(av-nmf19) allele and they support our previous finding that Protocadherin 15 plays an important role in hair-bundle morphogenesis.

Advanced bionics thin lateral and Helix II electrodes: a temporal bone study.

OBJECTIVE: This study was performed to evaluate the insertional properties of two cochlear implant electrodes recently developed by Advanced Bionics Corporation. STUDY DESIGN: Anatomic study using human cadaveric temporal bones. METHODS: The electrode prototypes we tested are the Thin Lateral and Helix II arrays, which incorporate features designed to minimize insertional trauma. A total of eight electrodes (4 of each prototype) were evaluated after insertion into freshly fixed temporal bones. The electrodes were inserted by way of standard cochleostomies, and the specimens were subsequently dissected to assess electrode position, insertion depth, and intracochlear trauma. RESULTS: Quantitative data regarding insertion depths and contact distances from the modiolus are presented for all electrodes tested. The mean insertion depths were 368 degrees for the Thin Lateral electrodes, which are designed to approximate the lateral cochlear wall, and 436 degrees for the Helix II electrodes, which occupy a more medial position in the scala tympani. No evidence of insertional trauma was observed with either electrode. The ease of insertion and absence of trauma were confirmed during additional trials in which electrode behavior was directly observed during insertion into previously opened cochleas. CONCLUSION: Both electrodes performed favorably in our human temporal bone trials, and both arrays appear promising for clinical use, especially in patients with residual hearing in whom atraumatic insertion is an important objective.

Spectrum of middle and inner ear abnormalities in infants with congenital heart defects.

OBJECTIVE: To evaluate temporal bone histopathology in infants with congenital heart defects (CHD). STUDY DESIGN AND SETTING: A retrospective review of our temporal bone collection was conducted to identify temporal bones acquired from infants with CHD. Subjects were divided into nonsyndromic and syndromic CHD groups. The presence of temporal bone abnormalities and the incidence of abnormalities that may result in hearing impairment were determined. RESULTS: Thirty-eight temporal bones obtained from 16 infants with nonsyndromic CHD and 4 with syndromic CHD were evaluated. Nonsyndromic CHD cases had abnormalities such as a mesenchymal remnant, malformed stapes, persistent stapedial artery, shallow round window, dehiscent facial nerve canal, short cochlea, strial basophilic deposits, deformity of the spiral ligament, bulging Reissner's membrane, hypoplastic lateral semicircular canal, and cupular deposits. Syndromic CHD cases had abnormalities including narrow round window niche, facial canal dehiscence, strial basophilic deposits and cysts, and outer hair cell loss. Middle and inner ear abnormalities that may impair hearing were observed in 6 subjects with nonsyndromic CHD and in 1 subject with syndromic CHD. CONCLUSIONS: A wide variety of temporal bone defects were documented in infants with CHD. Congenital middle and inner ear abnormalities should be anticipated in the hearing assessment and otologic surgery of infants with CHD.

Fixation of the stapes footplate in children: a clinical and temporal bone histopathologic study.

OBJECTIVE: To clarify the anatomic characteristics, cause, and surgical outcomes relating to fixation of the stapes footplate in children. STUDY DESIGN: Retrospective case review and four-center histopathologic study of temporal bones. SETTING: Tertiary referral center. PATIENTS: We reviewed charts and histologic specimens from 12 children, aged 7 to 13 years, who underwent surgery for footplate fixation. We also studied stapes footplates in 288 temporal bones from 181 children ranging from newborn (20-44 weeks of gestation) to 13 years of age. MAIN OUTCOME MEASURE: Anomalies of the stapes footplate in children. RESULTS: The average age of diagnosis of hearing loss was 6.6 years. Criteria for a diagnosis of otosclerosis were progression of a conductive hearing loss and an intraoperative finding of fixation of the anterior stapediovestibular joint in five patients. In contrast, a nonhomogeneous, thickened, fixed footplate and the absence of an annular ligament were indicators of congenital fixation in six children. In one child, there was neither new bone from the otic capsule nor any obvious otosclerotic foci. In the temporal bone study, 17 of 181 (9.4%) children had anomalies of the stapes footplates, with ankylosis in 4 (2.2%). In two subjects (1.1%), there was an otosclerotic focus not in contact with the stapes footplate. CONCLUSION: Children younger than 6 years with various congenital anomalies are more likely to have congenital footplate fixation, which will present intraoperatively as a thickened footplate with a partial or absent annular ligament. Children older than 6 years with progressive conductive hearing loss are more likely to have otosclerosis, which presents as fixation of the anterior stapediovestibular joint. The difference in surgical outcomes is probably related to different degrees of footplate abnormality.

Temporal bone histopathologic findings in partial trisomy 13 and partial trisomy 14.

OBJECTIVE: To describe temporal bone histopathology in an infant with partial trisomies of chromosomes 13 and 14. METHODS: Temporal bones were taken at autopsy from a 7-day-old neonate who has both partial trisomy 13 and partial trisomy 14. The right temporal bone was embedded in celloidin and sections were cut for microscopic examination. The left temporal bone was studied by microdissection. The middle ear was examined and the inner ear sensory organs dissected for study by light microscopy. RESULTS: The external auditory canal was stenotic in both ears. Remnants of mesenchymal tissue were present in the middle ear cavity. The middle ear ossicles were normal except that both stapes were malformed with a single crus and a small footplate. Both facial nerve canals were dehiscent in the region of the oval window. The cochlea was malformed bilaterally; a scala communis was present and the basilar membrane was abnormally short. No loss of sensory cells was observed in either cochlea. Blood vessels were found traversing scala vestibuli and there were cystic lesions in the stria vascularis and spiral ligament. In the middle cochlear turn, the bony wall of scala vestibuli and the osseous spiral lamina were covered by a substantial layer of connective tissue which appeared to be an extension of the spiral ligament. This is an unusual finding which, to the authors' knowledge, has not been previously reported. In the vestibular apparatus a wide communication was present between the saccule and utricle. CONCLUSIONS: As this study demonstrates, abnormalities of the external, middle, and inner ear may occur in cases of partial trisomy 13 and partial trisomy 14. Both temporal bone findings and clinical features in partial trisomy 13 and partial trisomy 14 to some degree overlap with those of trisomy 13, partial trisomy 13 and partial trisomy 14.

Temporal bone microdissection for anatomic study of cochlear implant electrodes.

OBJECTIVE: This report describes a temporal bone microdissection method for laboratory evaluation of cochlear implant electrodes. DESIGN: Anatomic study of human temporal bones. METHODS: Implant electrodes from three manufacturers were inserted into temporal bones which were processed and dissected so as to visualize spatial relationships between the electrodes and sensorineural structures of the cochlea. RESULTS AND CONCLUSION: Images are presented illustrating perimodiolar and lateral wall electrode arrays after insertion into the human cochlea and functional characteristics of the two electrode types are discussed. Temporal bone microdissection permits direct, three-dimensional study of inner ear structures and is an effective method for evaluation of the insertional properties of cochlear implant electrodes. Copyright (c) 2005 John Wiley & Sons, Ltd.

A new spontaneous mutation in the mouse Ames waltzer gene, Pcdh15.

A recessive deafness mutation in the mouse arose spontaneously and was identified in a colony segregating a null allele of the gastrin-releasing peptide receptor (Grpr) locus. Auditory-evoked brain stem response measurements revealed deafness in 7-week-old affected mice. By linkage analyses, the mutant phenotype was mapped near marker D10Mit186 and the protocadherin gene Pcdh15. As shown by complementation testing, the new mutation is allelic with Ames waltzer (Pcdh15(av)). Sequencing mutant-derived brain Pcdh15 cDNAs identified the insertion of a cytosine residue at nucleotide position c2099 (2099insC), which results in a frame-shift and premature stop codon. Abnormal stereocilia on inner and outer hair cells of the organ of Corti were identified by scanning electron microscopy as early as postnatal day 0 and cross-sectional histology revealed severe neuroepithelial degeneration in cochleas of 30-50-day-old mutants. The new allele of Ames waltzer, designated Pcdh15(av-Jfb), may aid in studying the histopathology associated with Usher syndrome type 1F, which is caused by a functional null allele of PCDH15.

The incidence and distribution of cupular deposits in the pediatric vestibular labyrinth.

OBJECTIVES: Deposits of basophilic material on the cupulae of the semicircular ducts have been described in adult human temporal bones, and such deposits have been implicated in the clinical phenomenon of benign paroxysmal positional vertigo (BPPV). Although relatively rare, BPPV has been reported to occur in children. The goal of this study was to evaluate the occurrence of cupular deposits in pediatric material. STUDY DESIGN: Basic science, two-center histopathologic temporal bone study. METHODS: We examined 186 temporal bones from 121 individuals between the ages of newborn and 10 years. The average age was 14.7 months. All temporal bones were acquired at autopsy, embedded in celloidin, and sectioned for light microscopic study. The cupulae of the semicircular ducts were identified and any deposits found were graded according to their size and position on the cupula. RESULTS: A total of 276 cupulae were identified, and in 35 (12.7%) of these a basophilic deposit was found. In many cases the deposits contained recognizable otoconial crystals. Most deposits were small and they were almost equally distributed between the three semicircular ducts. However, the lateral and posterior cupulae were somewhat more involved than the superior cupula. Our data showed that cupular deposits are less frequently found in the pediatric labyrinth, compared with adults as reported in previous studies. CONCLUSIONS: The lower occurrence in children versus adults suggests that the deposits may be a phenomenon of the aging vestibular labyrinth.

Cochlear degeneration in leigh disease: histopathologic features.

OBJECTIVE: To describe pathologic findings from temporal bones acquired from an infant with Leigh disease. STUDY DESIGN: Retrospective case review. MATERIALS AND METHODS: Temporal bones were taken at autopsy from an 8-month-old infant with Leigh disease. The right temporal bone was studied by microdissection. The middle ear was examined and the inner ear sensory organs dissected for study by light microscopy. The left temporal bone was embedded in celloidin, and sections were cut for microscopic examination. RESULTS: Middle ear structures were normal bilaterally. There was, however, evidence of otitis media in both middle ears, which was more severe on the left side. Inner and outer hair cell loss, patchy degeneration of organ of Corti, and loss of nerve fibers in the osseous spiral lamina were found in the basal and middle turns of both cochleas. Basophilic deposits in the stria vascularis were observed in the apical portion of the left cochlea. CONCLUSIONS: Inner ear sensorineural degeneration may occur in Leigh disease. Possible cochlear dysfunction caused by the degenerative changes needs to be considered in the hearing assessment of patients with Leigh disease.

Histopathological basis of hearing impairment in Wolf-Hirschhorn syndrome.

OBJECTIVES/HYPOTHESIS: To perform histological examination of temporal bones acquired from an infant with Wolf-Hirschhorn syndrome with an emphasis on identifying abnormalities that might be responsible for hearing impairment in this disorder. STUDY DESIGN: Retrospective case review. METHODS: Temporal bones were taken at autopsy from a 10-month-old infant with Wolf-Hirschhorn syndrome. The right-side temporal bone was studied by microdissection. The middle ear was examined, and the inner ear sensory organs dissected for study by light microscopy. The left-side temporal bone was embedded in celloidin, and sections were cut for microscopic examination. RESULTS: Chronic otitis media was observed in both ears. Inflammation, effusion, and adhesions were present in the middle ear space. The malleus was malformed, and the chorda tympani nerve was found to pass through the bone of the malleus bilaterally. There was an area of sharply defined outer hair cell loss in the lower basal turn of the right-side organ of Corti, and defects were noted in the bone of the apical osseous spiral lamina in both cochleae. CONCLUSION: In addition to the presence of otitis media, the likelihood of congenital abnormalities of the middle and inner ear should be considered in the assessment of patients with Wolf-Hirschhorn syndrome with hearing impairment.

Hearing loss is an early consequence of Npc1 gene deletion in the mouse model of Niemann-Pick disease, type C.

Niemann-Pick disease, type C1 (NPC1) is a rare lysosomal lipidosis that is most often the result of biallelic mutations in NPC1, and is characterized by a fatal neurological degeneration. The pathophysiology is complex, and the natural history of the disease is poorly understood. Recent findings from patients with NPC1 and hearing loss suggest that multiple steps along the auditory pathway are affected. The current study was undertaken to determine the auditory phenotype in the Npc1 (nih) mutant mouse model, to extend analyses to histologic evaluation of the inner ear, and to compare our findings to those reported from human patients. Auditory testing revealed a progressive high-frequency hearing loss in Npc1 (-/-) mice that is present as early as postnatal day 20 (P20), well before the onset of overt neurological symptoms, with evidence of abnormalities involving the cochlea, auditory nerve, and brainstem auditory centers. Distortion product otoacoustic emission amplitude and auditory brainstem response latency data provided evidence for a disruption in maturational development of the auditory system in Npc1 (-/-) mice. Anatomical study demonstrated accumulation of lysosomes in neurons, hair cells, and supporting cells of the inner ear in P30 Npc1 (-/-) mice, as well as increased numbers of inclusion bodies, myelin figures, and swollen nerve endings in older (P50-P70) mutant animals. These findings add unique perspective to the pathophysiology of NPC disease and suggest that hearing loss is an early and sensitive marker of disease progression.

Vascular trauma during cochlear implantation: a contributor to residual hearing loss?

OBJECTIVE: This study was performed to investigate the vascular structures of the cochlea that are potentially vulnerable to mechanical trauma during cochlear implant surgery. BACKGROUND: Despite improvements in surgical technique and electrode design, residual hearing is lost in a significant percentage of cochlear implant patients. Although a variety of factors may contribute, it is widely believed that mechanical trauma plays an important role. This study focused on the vasculature of scala tympani and its potential susceptibility to injury during implant surgery. METHODS: Anatomic study of normal human temporal bones prepared by either conventional cross sectioning or by microdissection for examination by light or scanning electron microscopy. RESULTS: Blood vessels located at or near the perilymphatic surface of scala tympani are predominately of the venous type, and they are situated so as to be at risk for trauma during implantation. Those vessels include veins on the lateral wall and floor of scala tympani, the modiolar wall and the undersurface of the osseous lamina and basilar membrane. CONCLUSION: Injury or occlusion of blood vessels associated with scala tympani may adversely affect inner ear function, potentially contributing to hearing loss following cochlear implantation.