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Introduction Cochlear implantation is an increasingly common procedure in the treatment of severe to profound sensorineural hearing loss (SNHL) in children and adults. It is often performed as a day-case procedure. The major drive towards day-case surgery has been from a logistical, economical and societal perspective, but we also speculate that the patient9s quality of life (QoL) is at least equal to inpatient surgery if not increased as a result of rapid discharge and rehabilitation. Even though cochlear implantation seems well suited to a day-case approach and this even seems to be common practice in some countries, evidence is scarce and of low quality to guide us towards the preferred treatment option. Methods and analysis A single-centre, non-blinded, randomised, controlled trial was designed to (primarily) investigate the effect on general QoL of day-case cochlear implantation compared to inpatient cochlear implantation and (secondarily) the effect of both methods on (subjective) hearing improvement, disease-specific QoL, tinnitus, vertigo and cost-effectiveness. 30 adult patients with severe to profound bilateral postlingual SNHL who are eligible for unilateral cochlear implantation will be randomly assigned to either the day-case or inpatient treatment group. The outcome measures will be assessed using auditory evaluations, questionnaires (preoperatively, at 1-week, 3-week, 3-month and 1-year follow-up) and costs diaries (weekly during the first month postoperatively, after which once in a month until 1-year follow-up). Preoperative and postoperative outcomes will be compared. The difference in costs and benefit will be represented using the incremental cost utility/effectiveness ratio. The analyses will be carried out on an intention-to-treat basis. Ethics and dissemination This research protocol was approved by the Institutional Review Board of the UMC Utrecht (NL45590.041.13; V.5, November 2015). The trial results will be disseminated through peer-reviewed medical journals and presented at scientific conferences. Trial registration number NTR4464; Pre-results.

Objective: This review aimed to evaluate the additional benefit of pediatric cochlear implantation before 12 months of age considering improved speech and language development and auditory performance. Materials and Methods: We conducted a search in PubMed, EMBASE and CINAHL databases and included studies comparing groups with different ages at implantation and assessing speech perception and speech production, receptive language and/or auditory performance. We included studies with a high directness of evidence (DoE). Results: We retrieved 3,360 articles. Ten studies with a high DoE were included. Four articles with medium DoE were discussed in addition. Six studies compared infants implanted before 12 months with children implanted between 12 and 24 months. Follow-up ranged from 6 months to 9 years. Cochlear implantation before the age of 2 years is beneficial according to one speech perception score (phonetically balanced kindergarten combined with consonant-nucleus-consonant) but not on Glendonald auditory screening procedure scores. Implantation before 12 months resulted in better speech production (diagnostic evaluation of articulation and phonology and infant-toddler meaningful auditory integration scale), auditory performance (Categories of Auditory Performance-II score) and receptive language scores (2 out of 5; Preschool Language Scale combined with oral and written language skills and Peabody Picture Vocabulary Test). Conclusions: The current best evidence lacks level 1 evidence studies and consists mainly of cohort studies with a moderate to high risk of bias. Included studies showed consistent evidence that cochlear implantation should be performed early in life, but evidence is inconsistent on all speech and language outcome measures regarding the additional benefit of implantation before the age of 12 months. Long-term follow-up studies are necessary to provide insight on additional benefits of early pediatric cochlear implantation.

Item does not contain fulltext OBJECTIVE: To study the cost-utility of simultaneous bilateral cochlear implantation (CI) versus unilateral CI. STUDY DESIGN: Randomized controlled trial (RCT). SETTING: Five tertiary referral centers. PATIENTS: Thirty-eight postlingually deafened adults eligible for cochlear implantation. INTERVENTIONS: A cost-utility analysis was performed from a health insurance perspective. MAIN OUTCOME MEASURES: Utility was assessed using the HUI3, TTO, VAS on hearing, VAS on general health and EQ-5D. We modeled the incremental cost per quality-adjusted life year (QALY) of unilateral versus bilateral CI over periods of 2, 5, 10, 25 years, and actual life-expectancy. RESULTS: Direct costs for unilateral and bilateral CI were euro43,883 +/- euro11,513(SD) and euro87,765 +/- euro23,027(SD) respectively. Annual costs from the second year onward were euro3,435 +/- euro1,085(SD) and euro6,871 +/- euro2,169(SD), respectively. A cost-utility analysis revealed that a second implant became cost-effective after a 5- to 10-year period, based on the HUI3, TTO, and VAS on hearing. CONCLUSION: This is the first study that describes a cost-utility analysis to compare unilateral with simultaneous bilateral CI in postlingually deafened adults, using a multicenter RCT. Compared with accepted societal willingness-to-pay thresholds, simultaneous bilateral CI is a cost-effective treatment for patients with a life expectancy of 5-10 years or longer.

Item does not contain fulltext IMPORTANCE: The cost of bilateral cochlear implantation (BCI) is usually not reimbursed by insurance companies because of a lack of well-designed studies reporting the benefits of a second cochlear implant. OBJECTIVE: To determine the benefits of simultaneous BCI compared with unilateral cochlear implantation (UCI) in adults with postlingual deafness. DESIGN, SETTING, AND PARTICIPANTS: A multicenter randomized clinical trial was performed. The study took place in 5 Dutch tertiary referral centers: the University Medical Centers of Utrecht, Maastricht, Groningen, Leiden, and Nijmegen. Forty patients eligible for cochlear implantation met the study criteria and were included from January 12, 2010, through November 2, 2012. The main inclusion criteria were postlingual onset of hearing loss, age of 18 to 70 years, duration of hearing loss of less than 20 years, and a marginal hearing aid benefit. Two participants withdrew from the study before implantation. Nineteen participants were randomized to undergo UCI and 19 to undergo BCI. INTERVENTIONS: The BCI group received 2 cochlear implants during 1 surgery. The UCI group received 1 cochlear implant. MAIN OUTCOMES AND MEASURES: The primary outcome was the Utrecht Sentence Test with Adaptive Randomized Roving levels (speech in noise, both presented from straight ahead). Secondary outcomes were consonant-vowel-consonant words in silence, speech-intelligibility test with spatially separated sources (speech in noise from different directions), sound localization, and quality of hearing questionnaires. Before any data were collected, the hypothesis was that the BCI group would perform better on the objective and subjective tests that concerned speech intelligibility in noise and spatial hearing. RESULTS: Thirty-eight patients were included in the study. Fifteen patients in the BCI group used hearing aids before implantation compared with 19 in the UCI group. Otherwise, there were no significant differences between the groups' baseline characteristics. At 1-year follow-up, there were no significant differences between groups on the Utrecht Sentence Test with Adaptive Randomized Roving levels (9.1 dB, UCI group; 8.2 dB, BCI group; P = .39) or the consonant-vowel-consonant test (median percentage correct score 85.0% in the UCI group and 86.8% in the BCI group; P = .21). The BCI group performed significantly better than the UCI group when noise came from different directions (median speech reception threshold in noise, 14.4 dB, BCI group; 5.6 dB, BCI group; P

Objectives: MYH9-related disease (MYH9-RD) is an autosomal-dominant disorder deriving from mutations in MYH9, the gene for the nonmuscle myosin heavy chain (NMMHC)-IIA. MYH9-RD has a complex phenotype including congenital features, such as thrombocytopenia, and noncongenital manifestations, namely sensorineural hearing loss (SNHL), nephropathy, cataract, and liver abnormalities. The disease is caused by a limited number of mutations affecting different regions of the NMMHC-IIA protein. SNHL is the most frequent noncongenital manifestation of MYH9-RD. However, only scarce and anecdotal information is currently available about the clinical and audiometric features of SNHL of MYH9-RD subjects. The objective of this study was to investigate the severity and propensity for progression of SNHL in a large series of MYH9-RD patients in relation to the causative NMMHC-IIA mutations. Design: This study included the consecutive patients diagnosed with MYH9-RD between July 2007 and March 2012 at four participating institutions. A total of 115 audiograms were analyzed from 63 patients belonging to 45 unrelated families with different NMMHCIIA mutations. Cross-sectional analyses of audiograms were performed. Regression analysis was performed, and age-related typical audiograms (ARTAs) were derived to characterize the type of SNHL associated with different mutations. Results: Severity of SNHL appeared to depend on the specific NMMHCIIA mutation. Patients carrying substitutions at the residue R702 located in the short functional SH1 helix had the most severe degree of SNHL, whereas patients with the p.E1841K substitution in the coiled-coil region or mutations at the nonhelical tailpiece presented a mild degree of SNHL even at advanced age. The authors also disclosed the effects of different amino acid changes at the same residue: for instance, individuals with the p.R702C mutation had more severe SNHL than those with the p.R702H mutation, and the p.R1165L substitution was associated with a higher degree of hearing loss than the p.R1165C. In general, mild SNHL was associated with a fairly flat audiogram configuration, whereas severe SNHL correlated with downsloping configurations. ARTA plots showed that the most progressive type of SNHL was associated with the p.R702C, the p.R702H, and the p.R1165L substitutions, whereas the p.R1165C mutation correlated with a milder, nonprogressive type of SNHL than the p.R1165L. ARTA for the p.E1841K mutation demonstrated a mild degree of SNHL with only mild progression, whereas the ARTA for the mutations at the nonhelical tailpiece did not show any substantial progression. Conclusions: These data provide useful tools to predict the progression and the expected degree of severity of SNHL in individual MYH9-RD patients, which is especially relevant in young patients. Consequences in clinical practice are important not only for appropriate patient counseling but also for development of customized, genotype-driven clinical management. The authors recently reported that cochlear implantation has a good outcome in MYH9-RD patients; thus, stricter follow-up and earlier intervention are recommended for patients with unfavorable genotypes. Fil: Verver, Eva J.J.. University of Utrecht; Países Bajos Fil: Topsakal, Vedat. University of Utrecht; Países Bajos Fil: Kunst, Henricus P. M.. Radboud University Medical Centre; Países Bajos Fil: Huygen, Patrick L. M.. Radboud University Medical Centre; Países Bajos Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Savoia, Anna. Università degli Studi di Trieste; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia Fil: Benazzo, Marco. Fondazione Policlinico San Matteo; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia Fil: Fierro, Tiziana. Università di Perugia; Italia Fil: Grolman, Wilko. University of Utrecht; Países Bajos Fil: Gresele, Paolo. Università di Perugia; Italia Fil: Pecci, Alessandro. Fondazione Policlinico San Matteo; Italia. Istituti di Ricovero e Cura a Carattere Scientifico; Italia. Università degli Studi di Pavia; Italia

The aim of this study was to describe the prevalence of specific audiogram configurations in a healthy, otologically screened population between 55 and 65 years old. The audiograms of 1147 subjects (549 males and 598 females between 55 and 65 years old) were collected through population registries and classified according to the configuration of hearing loss. Gender and noise/solvent-exposure effects on the prevalence of the different audiogram shapes were determined statistically. In our population 'Flat' audiograms were most dominantly represented (37%) followed by 'High frequency Gently sloping' audiograms (35%) and 'High frequency Steeply sloping' audiograms (27%). 'Low frequency Ascending' audiograms, 'Mid frequency U-shape' audiograms and 'Mid frequency Reverse U-shape' audiograms were very rare (together less than 1%). The 'Flat'-configuration was significantly more common in females, whereas the 'High frequency Steeply sloping'-configuration was more common in males. Exposure to noise and/or solvents did not change this finding. In addition, females with a 'Flat' audiogram had a significantly larger amount of overall hearing loss compared to males. Furthermore, our data reveal a significant association between the prevalence of 'High frequency Steeply sloping' audiograms and the degree of noise/solvent exposure, despite a relatively high proportion of non-exposed subjects showing a 'High frequency Steeply sloping' audiogram as well.

Contains fulltext : 70189.pdf (Publisher’s version ) (Closed access) Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

To determine the effect of cochlear implantation on tinnitus perception in patients with severe bilateral postlingual sensorineural hearing loss and to demonstrate possible differences between unilateral and bilateral cochlear implantation.Prospective study.Thirty-eight adult patients were included in this prospective study, as part of a multicenter randomized controlled trial investigating the benefits of bilateral cochlear implantation versus unilateral cochlear implantation. Pre- and postoperative tinnitus perception scores were evaluated, before and 1 year after implantation on three tinnitus questionnaires; the Tinnitus Handicap Inventory (THI), the Tinnitus Questionnaire (TQ), and a visual analogue scale for tinnitus burden.Before implantation, the tinnitus prevalence was 42.1% (16 of 38) in the whole study group. One year after implantation, the tinnitus questionnaire scores had decreased in 71.4% according to the TQ and 80.0% according to the THI. Tinnitus was induced after cochlear implantation in six patients, five in the bilateral and one in the unilateral group.Our study shows that cochlear implantation is effective in the reduction of tinnitus in patients with bilateral sensorineural hearing loss who suffered from preoperative tinnitus. Conversely, tinnitus may also increase or even be induced by the cochlear implantation itself. Cochlear implant candidates should be well informed about these possible consequences before undergoing surgery.2b.

Item does not contain fulltext MYH9-related disease (MYH9-RD) is a rare autosomal dominant disease caused by mutation of MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (NMMHC-IIA). MYH9-RD patients have macrothrombocytopenia and granulocyte inclusions (pathognomonic sign of the disease) containing wild-type and mutant NMMHC-IIA. During life they might develop sensorineural hearing loss, cataract, glomerulonephritis, and elevation of liver enzymes. One of the MYH9 mutations, p.R705H, was previously reported to be associated with DFNA17, an autosomal dominant non-syndromic sensorineural hearing loss without any other features associated. We identified the same mutation in two unrelated families, whose four affected individuals had not only hearing impairment but also thrombocytopenia, giant platelets, leukocyte inclusions, as well as mild to moderate elevation of some liver enzymes. Our data suggest that DFNA17 should not be a separate genetic entity but part of the wide phenotypic spectrum of MYH9-RD characterized by congenital hematological manifestations and variable penetrance and expressivity of the extra-hematological features.

Objective:To outline the management options and neurological complications associated with repeated traumatic falls that cause intrusion of bone-anchored hearing aid abutments.Case report:A three-year-old boy with coloboma, heart defects, atresia of nasal choanae, retarded growth, genital abnormalities, ear defects and deafness was fitted with a bone-anchored hearing aid for severe conductive hearing loss and congenital ear malformations. Six months later, a traumatic fall caused an intrusion injury which rendered the bone-anchored hearing aid abutment unusable. Without removing the original abutment, a second abutment was inserted on the same side to aid his hearing. Two years later, the child fell again and damaged his second bone-anchored hearing aid abutment. Having been offered a surgical option to repair the area, the parents opted to keep the abutments in situ.Conclusion:Direct trauma to the fixture of a bone-anchored hearing aid is a relatively common long-term complication in children which can disrupt osseointegration and disable the implant. For young children who are either prone to falling or have behavioural problems, a bone-anchored hearing aid Softband may be more appropriate to non-invasively aid hearing.

To evaluate the influence of the introduction of newborn hearing screening programs on the age at cochlear implantation in children.Retrospective, multicenter cohort study.All 1,299 pediatric cochlear implant users who received their implants before the age of 5 years between 1995 and 2011 in the Medical University Hannover, Germany and University Medical Center Utrecht, the Netherlands were enrolled in this study. Age at implantation and the number of children implanted within the first year of life was assessed for each center.Age at cochlear implantation gradually declined over the years in both centers. The introduction of the screening resulted in significant decline in the age at implantation in the Netherlands; simultaneously, the number of children implanted within their first year of life increased significantly. Comparing 4-year epochs immediately before and after introduction of the screening, the mean age decreased from 2.4 to 1.2 years, and the percentage of early implanted children increased from 9% to 37%. In the German population, a similar effect of the introduction of the hearing screening program was absent.The introduction of the national newborn hearing screening program has reduced the age at cochlear implantation in young children in the Netherlands but not in Germany. Correspondingly, it resulted in an increase in the number of children implanted early in life. The difference between the Dutch and German population might be due to differences in the follow-up and referral after the hearing screening.

Item does not contain fulltext OBJECTIVE: To evaluate karyotype-specific ear and hearing problems in young-adult patients with Turner syndrome (TS) and assess the effects of previous treatment with oxandrolone (Ox). STUDY DESIGN: Double-blind follow-up study. SETTING: University hospital. PATIENTS: Sixty-five TS patients (mean age, 24.3 yr) previously treated with growth hormone combined with placebo, Ox 0.03 mg/kg per day, or Ox 0.06 mg/kg per day from the age of 8 years and estrogen from the age of 12 years. INTERVENTION: Ear examination was performed according to standard clinical practice. Air- and bone conduction thresholds were measured in decibel hearing level. MAIN OUTCOME MEASURES: We compared patients with total monosomy of the short arm of the X chromosome (Xp), monosomy 45,X and isochromosome 46,X,i(Xq), with patients with a partial monosomy Xp, mosaicism or other structural X chromosomal anomalies. We assessed the effect of previous Ox treatment. RESULTS: Sixty-six percent of the patients had a history of recurrent otitis media. We found hearing loss in 66% of the ears, including pure sensorineural hearing loss in 32%. Hearing thresholds in patients with a complete monosomy Xp were about 10 dB worse compared with those in patients with a partial monosomy Xp. Air- and bone conduction thresholds were not different between the placebo and Ox treatment groups. CONCLUSION: Young-adult TS individuals frequently have structural ear pathology, and many suffer from hearing loss. This indicates that careful follow-up to detect ear and hearing problems is necessary, especially for those with a monosomy 45,X or isochromosome 46,X,i(Xq). Ox does not seem to have an effect on hearing.

Summary Heterotopic salivary gland tissue (HSGT) is a rare finding in the lower neck. Bilateral lesions are even more exceptional. It is generally accepted HSGT originates from defective embryogenesis within the branchial apparatus and are closely related to branchial cysts and sinuses. The true aetiology however is not fully understood. Here we report a rare case with bilateral lesions in the neck that drained a clear substance after drinking. Surgical resection of a 2 cm upwards fistula tracks was performed under general anaesthesia. Microscopic examination of resection peaces showed arguments for HSGT on both sides. Several aetiological theories are also discussed.

Until 1993 it was commonly accepted that regeneration of vestibular hair cells was not possible in mammals. Two histological studies then showed structural evidence for spontaneous regeneration of vestibular hair cells after gentamicin treatment. There is less evidence for functional recovery going along with this regenerative process; in other words, do regenerated hair cells function adequately? This study aims to address this question, and in general evaluates whether spontaneous functional recovery may occur, in the short or long term, in mammals after ototoxic insult. Guinea pigs were treated with gentamicin for 10 consecutive days at a daily dose of 125 mg/kg body weight. Survival times varied from 1 day to 16 weeks. Vestibular short-latency evoked potentials (VsEPs) to linear acceleration pulses were recorded longitudinally to assess otolith function. After the final functional measurements we performed immunofluorescence histology for hair cell counts. Auditory brainstem responses (ABRs) to click stimuli were recorded to assess cochlear function. As intended, gentamicin treatment resulted in significant loss of utricular hair cells and accompanying declines in VsEPs. Hair cell counts 8 or 16 weeks after treatment did not significantly differ from counts after shorter survival periods. Maximal functional loss was achieved 1-4 weeks after treatment. After this period, only 2 animals showed recovery of VsEP amplitude - all other animals did not reveal signs of regeneration or recovery. In contrast, after initial ABR threshold shifts there was a small but significant recovery. We conclude that spontaneous recovery of otolith function, in contrast to cochlear function, is very limited in guinea pigs. These results support the concept of intratympanic gentamicin treatment where gentamicin is used for chemoablation of the vestibular sensory epithelia.

Item does not contain fulltext OBJECTIVE: To investigate the familial correlations and intraclass correlation of age-related hearing impairment (ARHI) in specific frequencies. In addition, heritability estimates were calculated. STUDY DESIGN: Multicenter survey in 8 European centers. SUBJECTS: One hundred ninety-eight families consisting of 952 family members, screened by otologic examination and structured interviews. Subjects with general conditions, known to affect hearing thresholds or known otologic cause were excluded from the study. RESULTS: We detected familial correlation coefficients of 0.36, 0.37, 0.36, and 0.30 for 0.25, 0.5, 1, and 2 kHz, respectively, and correlation coefficients of 0.20 and 0.18 for 4 and 8 kHz, respectively. Variance components analyses showed that the proportion of the total variance attributable to family differences was between 0.32 and 0.40 for 0.25, 0.5, 1, and 2 kHz and below 0.20 for 4 and 8 kHz. When testing for homogeneity between sib pair types, we observed a larger familial correlation between female than male subjects. Heritability estimates ranged between 0.79 and 0.36 across the frequencies. DISCUSSION: Our results indicate that there is a substantial shared familial effect in ARHI. We found that familial aggregation of ARHI is markedly higher in the low frequencies and that there is a trend toward higher familial aggregation in female compared with male subjects.

Objectives: The goals of the present study were twofold: in the first part, the prevalence and profile of hearing disability in healthy, middle-aged persons were determined by the speech, spatial, and qualities of hearing scale (SSQ). In the second part of this study, the number of SSQ items was reduced to five to make this questionnaire available for routine usage in clinical settings and for screening purposes. Methods: SSQ responses derived from 103 normal-hearing 18- to 25-year-old persons were compared with the SSQ responses of 24 clinically normal-hearing (all thresholds between 125 and 8000 Hz

BACKGROUND: Vestibular schwannomas (VSs) are the most common cerebellopontine angle tumors, accounting for 75% of all lesions in this location. OBJECTIVE: To evaluate the results after removal of VS through the enlarged translabyrinthine approach, which is a widening of the classic translabyrinthine approach that gives larger access and provides more room to facilitate tumor removal and to minimize surgery-related morbidities. METHODS: This was a retrospective study of 1865 patients who underwent VS excision through the enlarged translabyrinthine approach between 1987 and 2009. Mean age was 50.39 years. Mean tumor size was 1.8 cm. Median follow-up was 5.7 years. RESULTS: Total removal was achieved in 92.33% of cases; 143 patients had incomplete resection with evidence of regrowth in 8. In the 1742 previously untreated patients, anatomic preservation of facial nerve was achieved in 1661 cases (95.35%), and House-Brackmann grade I or II was reached in 1047 patients (59.87%). Facial nerve outcome was significantly better in tumors ≤ 20 mm. Surgical complications included cerebrospinal fluid leakage in 0.85%, meningitis in 0.10%, intracranial bleeding in 0.80%, non--VII/VIII cranial nerve palsy in 0.96%, cerebellar ataxia in 0.69%, and death in 0.10%. The technical modifications that evolved with increasing experience are described. CONCLUSION: The enlarged translabyrinthine approach is a safe and effective approach for the removal of VS. In our experience, the complication rate is very low and tumor size is still the main factor influencing postoperative facial nerve function with a cutoff point at around 20 mm.

Objectives: The objective of this study was to assess the differences in the recurrence rates of vestibular schwannoma (VS) after total tumor removal through enlarged translabyrinthine (ETL), retrosigmoid (RS), and middle cranial fossa (MCF) approaches. Our results were compared with previously published data, and literature reviews were done to identify the possible causes for the recurrence of VS. Methods: We performed a retrospective analysis of 2,400 cases of VS that underwent removal at the Gruppo Otologico, Piacenza, Italy, from 1983 until 2010. The minimum postoperative follow-up was 12 months. We also reviewed the previously published data on recurrence rates of VS after ETL, RS, and MCF approaches. Results: Total tumor removal was achieved in 2,252 cases (93.8%). The recurrence rate was 0.05% for the ETL approach, 0.7% for the RS approach, and 1.8% for the MCF approach. Literature reviews of 3 previously published case series utilizing the translabyrinthine approach showed that none of the primary tumors were less than 2.0 cm in size. Recurrences were seen between 1 and 13 years after the initial surgery. Conclusions: The rate of VS recurrence after total removal is exceptionally low in experienced hands. Undetected microscopic deposits left on crucial points such as the facial nerve, the preserved cochlea nerve, or the fundus of the internal auditory canal could be possible causes for the recurrence. A definite advantage of an ETL approach is the excellent internal auditory canal exposure, resulting in an extremely low rate of VS recurrence. The patients should be followed up to 15 years with gadolinium-enhanced magnetic resonance imaging (with fat suppression sequence in ETL approach cases). Recurrent VS may exhibit a faster growth rate than primary VS.

Universiteits-Biblioteek Your Subscriptions Logo Vol. 15, No. 4, 2010 Free Abstract Article (Fulltext) Article (PDF 406 KB) Original Paper Genotype-Phenotype Correlation for DFNA22: Characterization of Non-Syndromic, Autosomal Dominant, Progressive Sensorineural Hearing Loss due to MYO6 Mutations Vedat Topsakala, c, Nele Hilgertb, Joost van Dintherd, Lisbeth Tranebjærge, f, Nanna D. Rendtorffe, Andrzej Zarowskid, Erwin Offeciersd, Guy Van Campb, Paul van de Heyningc aDepartment of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; bDepartment of Medical Genetics, University of Antwerp, and cDepartment of Otorhinolaryngology, Antwerp University Hospital, University of Antwerp, Antwerp, and dUniversity ENT Department, Sint-Augustinus Hospital, Wilrijk, Antwerp, Belgium; eWilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, and fDepartment of Audiology, Bispebjerg Hospital, Copenhagen, Denmark Address of Corresponding Author Audiol Neurotol 2010;15:211-220 (DOI: 10.1159/000255339) goto top of page Key Words * Age-related typical audiograms * DFNA22 * Myosin VI * Autosomal dominant sensorineural hearing loss * Hereditary hearing impairment goto top of page Abstract Clinical and audiological examination was done in 2 Belgian families with autosomal dominant sensorineural hearing loss (SNHL) linked to DFNA22. Nineteen subjects in family 1 had mild to moderate SNHL starting in the third decade. The hearing loss was characterized by a flat audiogram affecting all tested frequencies with statistically significant progression. In family 2 eleven subjects were affected with mild to moderate SNHL starting in the second decade. Most of them showed a flat audiogram, but some had mid-frequency hearing loss. Significant progression of thresholds was present at 4 and 8 kHz. For all hitherto known DFNA22 families the audiological and clinical characteristics were correlated with the molecular data. This study describes the phenotype of 2 Belgian families with SNHL linked to DFNA22, both with a pathogenic change in the deafness gene MYO6. The phenotypes of all hitherto reported DFNA22 families with mutations in the MYO6 gene have been studied and compared. It seems that genetic defects that spare the motor domain of the myosin VI protein have a milder phenotype.

Objective: To study postoperative status of the mastoid cavity after cochlear implantation by the suprameatal approach method. Methods: Pre- and postoperative protocolair prepared CT-scans of the mastoid cavity of patients who were operated for cochlear implantation were studies. 79 patients were included in this study. All patients were operated by the two authors using a mastoid saving surgical suprameatal approach for cochlear implantation, The postoperative CT-scans were evaluated after 6 months or more after surgery. Changes of the state of the mastoid observed by CT scan were documented. Results: In 76 cases no abnormalities were observed in the mastoid of the operated ear for cochlear implantation. The delicate structures of the mastoid cavity were kept intact without any sign of mucosal reaction. In two cases of implantation for deafness due to otosclerosis swollen mucosa was observed in the mastoid without any clinical relevance. In one case (a child) opicafication of the whole mastoid and middle ear was observed without destruction of the structures of the mastoid. Treatment with oral antibiotics cured this otitis media without rest reactions in the mastoid . Conclusions: The delicate structures of the mastoid cavity can be kept intact using a mastoid saving suprameatal surgical approach in cochlear implant surgery, In almost all the cases we could demonstrate by CT-scan that there is not any reaction of the mucosa in the mastoid and middle ear after cochlear implantation. There were no differences in the postoperative state of the small or large pneumatized mastoid.

This study describes the heritability of audiometric shape parameters and the familial aggregation of different types of presbycusis in a healthy, otologically screened population between 50 and 75 years old. About 342 siblings of 64 families (average family-size: 5.3) were recruited through population registries. Audiometric shape was mathematically quantified by objective parameters developed to measure size, slope, concavity, percentage of frequency-dependent and frequency-independent hearing loss and Bulge Depth. The heritability of each parameter was calculated using a variance components model. Logistic regression models were used to estimate the odds ratios (ORs). Estimates of sibling recurrence risk ratios (lambda(s)) are also provided. Heritability estimates were generally higher compared to previous studies. ORs and lambda(s) for the parameters Total Hearing Loss (size), Uniform Hearing Loss (percentage of frequency-dependent hearing loss) and Bulge Depth suggest a higher heredity for severe types of presbycusis compared to moderate or mild types. Our results suggest that the separation of the parameter 'Total Hearing Loss' into the two parameters 'Uniform Hearing Loss' and 'Non-uniform Hearing Loss' could lead to the discovery of different genetic subtypes of presbycusis. The parameter 'Bulge Depth', instead of 'Concavity', seemed to be an important parameter for classifying subjects into 'susceptible' or 'resistant' to societal or intensive environmental exposure.

Contains fulltext : 70730.pdf (Publisher’s version ) (Closed access) Age-related hearing impairment (ARHI) is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. The contribution of various environmental factors has been relatively extensively studied. In contrast, investigations to identify the genetic risk factors have only recently been initiated. In this paper we describe the results of an association study performed on 2418 ARHI samples derived from nine centers from seven European countries. In 70 candidate genes, a total of 768 tag single nucleotide polymorphisms (SNPs) were selected based on HAPMAP data. These genes were chosen among the monogenic hearing loss genes identified in mice and men in addition to several strong functional candidates. After genotyping and data polishing, statistical analysis of all samples combined resulted in a P-value that survived correction for multiple testing for one SNP in the GRHL2 gene. Other SNPs in this gene were also associated, albeit to a lesser degree. Subsequently, an analysis of the most significant GRHL2 SNP was performed separately for each center. The direction of the association was identical in all nine centers. Two centers showed significant associations and a third center showed a trend towards significance. Subsequent fine mapping of this locus demonstrated that the majority of the associated SNPs reside in intron 1. We hypothesize that the causative variant may change the expression levels of a GRHL2 isoform.

Hearing loss is the most common sensory disorder, affecting 1 in 650 newborns. Linkage analysis revealed linkage to locus DFNA22 in two Belgian families 1 and 2 with autosomal dominant sensorineural hearing loss. As MYO6 has previously been reported as responsible for the hearing loss at loci DFNA22 and DFNB37, respectively, DNA sequencing of the coding region and the promoter of MYO6 was performed but this analysis did not reveal any mutations. However, only in patients of family 2, an insertion of 108 bp was identified in the mRNA of the gene. The inserted fragment was part of intron 23 and sequencing of this intron revealed a new splice-site mutation c.IVS23+2321T>G, segregating with the hearing loss in the family. The mutation causes a frameshift and a premature termination codon, but real-time PCR revealed that only 15-20% of the mRNA is degraded by nonsense-mediated decay, while the other part may give rise to an aberrant protein. In family 1, a quantitative real-time PCR experiment revealed a 1.5-1.8-fold overexpression of MYO6 in patients compared to controls. The possible presence of a gene duplication could be excluded by real-time PCR on genomic level. Most likely, the overexpression is caused by a mutation in an unidentified regulatory region of the gene. This study indicates that the inner ear hair cells are sensitive to changes in expression levels of MYO6.

A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (

Contains fulltext : 53710.pdf (Publisher’s version ) (Closed access) BACKGROUND: Age-related hearing impairment (ARHI) is the most common sensory impairment in older people, affecting 50% of those aged 80 years. The proportion of older people is increasing in the general population, and as a consequence, the number of people affected with ARHI is growing. ARHI is a complex disorder, with both environmental and genetic factors contributing to the disease. The first studies to elucidate these genetic factors were recently performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4. METHODS: In the present study, the association between ARHI and polymorphisms in genes that contribute to the defence against reactive oxygen species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from seven different countries and were combined into two test population samples, the general European population and the Finnish population. Two distinct phenotypes for ARHI were studied, Z(low) and Z(high), representing hearing in the low and high frequencies, respectively. Statistical analysis was performed for single polymorphisms (GSTM1, GSTT1, NAT2*5A, NAT2*6A, and NAT2*7A), haplotypes, and gene-environment and gene-gene interactions. RESULTS: We found an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in the general European population sample. The latter finding replicates previously published data. CONCLUSION: As replication is considered the ultimate proof of true associations in the study of complex disorders, this study provides further support for the involvement of NAT2*6A in ARHI.

The Advanced Bionics® (AB)-York crescent of sound is a new test setup that comprises speech intelligibility in noise and localization tests that represent everyday listening situations. One of its tests is the Sentence Test with Adaptive Randomized Roving levels (STARR) with sentences and noise both presented from straight ahead. For the Dutch population, we adopted the AB-York setup and replaced the English sentences with a validated set of Dutch sentences. The Dutch version of the STARR is called the Utrecht-STARR (U-STARR). This study primarily assesses the validity and reliability of the U-STARR compared to the Plomp test, which is the current Dutch gold standard for speech-in-noise testing. The outcome of both tests is a speech reception threshold in noise (SRTn). Secondary outcomes are the SRTn measured with sounds from spatially separated sources (SISSS) as well as sound localization capability. We tested 29 normal-hearing adults and 18 postlingually deafened adult patients with unilateral cochlear implants (CI). This study shows that the U-STARR is adequate and reliable and seems better suited for severely hearing-impaired persons than the conventional Plomp test. Further, CI patients have poor spatial listening skills, as demonstrated with the AB-York test.

Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Zhigh and Zlow, a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p-values for two SNPs for Zhigh—SNP9 (NT_004511:g.11244177A>T) and SNP15 (NT_004511:g.11257005C>T; NP_004691:p.Ala259Ala), and one SNP for Zlow—SNP12 (NT_004511:g.11249550A>T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNPs, resulting in three LD-blocks. LD-block 1 contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A>G) to SNP18 (NT_004511:g.11257509G>A; NP_004691:p.Thr293Thr), and LD-block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNPs of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene. Hum Mutat 27(10), 1007–1016, 2006. © 2006 Wiley-Liss, Inc.

Objective: To report the preoperative audiometric profile of surgically confirmed otosclerosis. Study Design: Retrospective, multicenter study. Setting: Four tertiary referral centers. Patients: One thousand sixty-four surgically confirmed patients with otosclerosis. Interventions: Therapeutic ear surgery for hearing improvement. Main Outcome Measures: Preoperative audiometric air conduction (AC) and bone conduction (BC) hearing thresholds were obtained retrospectively for 1064 patients with otosclerosis. A cross-sectional multiple linear regression analysis was performed on audiometric data of affected ears. Influences of age and sex were analyzed and age-related typical audiograms were created. Bone conduction thresholds were corrected for Carhart effect and presbyacusis; in addition, we tested to see if separate cochlear otosclerosis component existed. Corrected thresholds were than analyzed separately for progression of cochlear otosclerosis. Results: The study population consisted of 35% men and 65% women (mean age, 44 yr). The mean pure-tone average at 0.5, 1, and 2 kHz was 57 dB hearing level. Multiple linear regression analysis showed significant progression for all measured AC and BC thresholds. The average annual threshold deterioration for AC was 0.45 dB/yr and the annual threshold deterioration for BC was 0.37 dB/yr. The average annual gap expansion was 0.08 dB/year. The corrected BC thresholds for Carhart effect and presbyacusis remained significantly different from zero, but only showed progression at 2 kHz. Conclusion: The preoperative audiological profile of otosclerosis is described. There is a significant sensorineural component in patients with otosclerosis planned for stapedotomy, which is worse than age-related hearing loss by itself. Deterioration rates of AC and BC thresholds have been reported, which can be helpful in clinical practice and might also guide the characterization of allegedly different phenotypes for familial and sporadic otosclerosis.

Contains fulltext : 49141.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Genotype a family trait with autosomal dominant nonsyndromic sensorineural hearing impairment guided only by the phenotype. STUDY DESIGN: Family study. SETTING: Tertiary referral center. PATIENTS: Fifteen family members. METHODS: In the first phase, sequence analysis was performed on DNA isolated from buccal swabs of the proband and her daughter, guided by the phenotype based on audiometric data that were already available. After detection of the W276S missense mutation in the KCNQ4 gene in both patients, this finding was confirmed in the other affected family members. All participants completed a questionnaire, were clinically examined, and underwent standard pure-tone audiometry. The results were analyzed to refine the phenotypic features of the family trait. RESULTS: All clinically affected participants were carriers of the W276S hotspot mutation in exon 5 of the KCNQ4 gene on chromosome 1p34. Refined phenotypic features confirmed previously described phenotypes of DFNA2 families. CONCLUSIONS: Phenotype determination can be cost saving and very effective in detecting the genotype of autosomal dominant nonsyndromic hearing impairment, especially when phenotype analyses can be performed on data that are already available or easily collected.

BACKGROUND: MYH9-related disease (MYH9-RD) is a rare syndromic disorder deriving from mutations in MYH9, the gene for the heavy chain of non-muscle myosin IIA. Patients present with congenital thrombocytopenia and giant platelets and have a variable risk of developing sensorineural deafness, kidney damage, presenile cataract, and liver abnormalities. Almost all MYH9-RD patients develop the hearing defect, which, in many individuals, progresses to severe to profound deafness with high impact on quality of life. These patients are potential candidates for cochlear implantation (CI), however, no consistent data are available about the risk to benefit ratio of CI in MYH9-RD. The only reported patient who received CI experienced perisurgery complications that have been attributed to concurrent platelet defects and/or MYH9 protein dysfunction. METHODS: By international co-operative study, we report the clinical outcome of 10 patients with MYH9-RD and severe to profound deafness who received a CI at 8 institutions.RESULTS: Nine patients benefited from CI: in particular, eight of them obtained excellent performances with restoration of a practically normal hearing function and verbal communication abilities. One patient had a slightly worse performance that could be explained by the very long duration of severe deafness before CI. Finally, one patient did not significantly benefit from CI. No adverse events attributable to MYH9-RD syndrome were observed, in particular no perisurgery bleeding complications due to the platelet defects were seen. Patients' perioperative management is described and discussed. CONCLUSIONS: CI is safe and effective in most patients with MYH9-RD and severe to profound deafness and should be offered to these subjects, possibly as soon as they develop the criteria for candidacy.

Objective: To report on the professional repercussions of an intravestibular schwannoma in a commercial airline pilot. Patients: The case of a single patient with a unilateral intravestibular schwannoma. Intervention: Return to a flying status with specific restrictions and under tight conditions depending on the outcomes of a mandatory periodic watch-and-rescan policy. Main Outcome Measures: Consecutive magnetic resonance imaging results coupled to the clinical otovestibular status of the patient. Results: After 16 uneventful months of flying, the pilot was grounded after a first episode of vertigo. Conclusion: The combination of an intravestibular schwannoma-as one of the rarest intralabyrinthine schwannomas-and a pilot-for whom proper otovestibular functioning is of the uppermost importance-challenges the responsibilities of all involved. Depending on the clinical circumstances and under tight conditions with specific restrictions, a return to a flying status can very exceptionally be considered. An open discussion and the establishment of a relation of mutual trust are felt to be an absolute prerequisite.