Mastoid obliteration with hydroxyapatite vs. bone pâté in mastoidectomy surgery performed on patients with cholesteatoma and chronic suppurative otitis media: a retrospective analysis.

PURPOSE: To compare the efficacy and safety of hydroxyapatite vs. bone pâté as obliteration material in mastoidectomy surgery for patients with chronic suppurative otitis media and cholesteatoma. METHODS: This is a retrospective, multi-center, cohort study. All patients were followed up with micro-otoscopy, audiometry, and, if indicated, MRI with diffusion-weighted imaging. The following outcome parameters were analyzed: procedure safety (wound infections and complications), cholesteatoma recidivism rates (residual/recurrent), control of infection (Merchant's scale), and hearing results (pure-tone averages at 500/1000/2000/4000 Hz). RESULTS: Eighty-three cases were included: 45 obliterated with hydroxyapatite and 38 with bone pâté, with a mean follow-up time of, respectively, 25 and 24 months. Wound infections were only detected in the bone pâté group (4.8%) and successfully treated with oral or intravenous antibiotics and surgical drainage (p = 0.026). No other major surgical complications were observed in both groups. Cholesteatoma recidivism was observed in 15% using hydroxyapatite and 12% using bone pâté (p = 0.471). Complete control of infection (Merchant 0) was achieved in 76.2% using bone pâté and 86.8% using hydroxyapatite at 12 months postoperatively (p = 0.223). All patients showed good postoperative healing without complete failure to manage infection (Merchant 3). Pre- and postoperative audiometry showed significant improvement in hearing results in both groups. No significant difference between the obliteration materials was observed. CONCLUSIONS: Evaluation of mastoid obliteration reveals that hydroxyapatite and bone pâté are safe and effective obliteration materials, with high success rates in achieving a dry ear, low recidivism rates, and good hearing outcome, respecting the short-term limitation. In addition, our study shows that hydroxyapatite results in fewer postoperative wound infections compared to bone pâté.

Percutaneous bone-anchored hearing implant surgery: linear incision technique with tissue preservation versus linear incision technique with tissue reduction.

OBJECTIVES: To identify differences in skin thickening and soft tissue reactions between the linear incision technique with tissue reduction (LITT-R) and the linear incision technique with tissue preservation (LITT-P). STUDY DESIGN: Retrospective cohort study. METHODS: All adult patients who underwent the LITT-R or LITT-P between August 2005 and December 2016 at a large general teaching hospital with a minimum follow-up of 6 months were included. RESULTS: A total of 83 implants were included using the LITT-R with a median follow-up of 74.0 months. In the LITT-P cohort 58 implants were included with a median follow-up of 16.5 months. Skin thickening was seen in seven implants (8.4%) in LITT-R cohort and 11 implants (19.0%) in the LITT-P cohort in the first 2 years of follow-up (p = 0.024). Skin thickening in need of treatment was registered in 5 (6.0%), respectively, 6 (10.3%) implants (p = 0.100). Moreover, treatment was successful in all cases. A soft tissue reaction (Holgers ≥ 1) was noticed in 28 (33.7%) implants in the LITT-R group compared to 16 implants (27.6%) in the LITT-P group (p = 0.679). An adverse soft tissue reaction (Holgers ≥ 2) was registered in 16 (19.2%), respectively, 2 (3.4%) implants. This difference was significant (p = 0.040). CONCLUSION: LITT-P has a significantly higher rate of skin thickening and LITT-R has a significantly higher proportion of adverse soft tissue reactions. Nevertheless, combined with the advantages of LITT-P described in other studies, this can be advocated as the preferred technique.

Clinical Outcomes of Soft Tissue Preservation Surgery With Hydroxyapatite-Coated Abutments Compared to Traditional Percutaneous Bone Conduction Hearing Implant Surgery-A Pragmatic Multi-Center Randomized Controlled Trial.

Background: Soft tissue preservation using a hydroxyapatite-coated abutment in bone conduction hearing implant surgery may lead to improved clinical outcomes over the short (1 year) and long term (3 years). Methods: In this open multi-center, randomized (1:1), controlled clinical trial, subjects with conductive, mixed hearing loss or single-sided sensorineural deafness were randomly assigned to receive the conventional intervention, a titanium abutment with soft tissue reduction surgery (control), or a new intervention, a hydroxyapatite-coated abutment with soft tissue preservation surgery (test). The primary efficacy outcome was the combined endpoint of numbness, pain, peri-abutment dermatitis, and soft tissue thickening/overgrowth after 1 and 3 years. Results: The Intention-to-treat (ITT) population consisted of 52 control subjects and 51 test subjects. The difference between the groups after 1 year of follow-up as measured by the primary efficacy outcome was not statistically significant (p = 0.12) in the ITT population (n = 103), but did reach statistical significance (p = 0.03) in the per-protocol (PP) population (n = 96). It showed an advantage for the test group, with over twice as many subjects (29%) without these medical events during the first year compared to the control group (13%). After 3 years, the difference between the two groups had declined and did not reach statistical significance (24 vs. 10%, ITT p = 0.45). Secondary outcome measures which showed a statistical significant difference during the first year, such as surgical time (15 vs. 25 minutes, p < 0.0001), numbness (90 vs. 69% of subjects experienced no numbness at 1 year, p < 0.01), neuropathic pain at 3 months (p = 0.0087) and the overall opinion of the esthetic outcome (observer POSAS scale at 3 months, p < 0.01) were favorable for the test group. More soft tissue thickening/overgrowth was observed at 3 weeks for the test group (p = 0.016). Similar results were achieved for the long term follow up. Conclusions: Soft tissue preservation with a hydroxyapatite-coated abutment leads to a reduction in the combined occurrence of complications over the first year which is not statistically significant in the ITT population but is in the PP population. This effect decreased for the long-term study follow up of 3 years and did also not reach statistical significance.

[Diagnostic image (271). A woman with blue sclerae, brittle bones and hearing loss]. / Diagnose in beeld (271). Een vrouw met blauwe sclerae, broos beenstelsel en gehoorklachten.

A 51-year-old woman presented with blue sclerae, brittleness of the bones and hearing loss due to osteogenesis imperfecta with ear involvement: Van der Hoeve-De Kleyn syndrome.

[From gene to disease; a progressive cochlear-vestibular dysfunction with onset in middle-age (DFNA9)]. / Van gen naar ziekte; een op middelbare leeftijd optredende progressieve cochleavestibulaire disfunctie (DFNA9).

DFNA9 is an autosomal dominant genetic inner-ear hearing impairment that starts to show itself in the 3rd and 4th decades of life. This hearing impairment may be of a different degree of severity in each ear. Progression of hearing loss is about 3 dB/year. In about one in three patients severe vestibular symptoms similar to those in Ménière's disease are present as a result of a progressive impairment of the vestibular system. Several mutations were found in the COCH-gene on chromosome 14. There are indications that some of the mutations disrupt the folding of the cochlin protein, an important component of the extracellular matrix in the inner ear. DNA-diagnostics confirming the diagnosis ofDFNA9 are possible.

Familial progressive vestibulocochlear dysfunction caused by a COCH mutation (DFNA9).

OBJECTIVE: To describe the decline of vestibulocochlear function in a man with vestibulocochlear dysfunction caused by a Pro51Ser mutation within the COCH gene on chromosome 14q12-13 (DFNA9). METHODS: A follow-up of more than 15 years was performed in a single case. Clinical investigations were supplemented by oculomotor, vestibular, and auditory tests. RESULTS: A 50-year-old man had had progressive sensorineural hearing loss and dysequilibrium for 15 years; he had been asymptomatic at the age of 35 years. He suffered from instability in the dark, head movement-dependent oscillopsia, paroxysmal positional vertigo, and vertigo with and without nausea. Hearing impairment started unilaterally, predominantly in the high frequencies. He also reported tinnitus. Disease progressed to severe bilateral high-frequency hearing impairment and vestibular areflexia. Fluctuation of vestibulocochlear function was documented and mentioned by the patient. CONCLUSIONS: Our patient proved to suffer from an autosomal dominant vestibulocochlear disorder caused by a COCH gene mutation. The remarkable medical history has some features in common with Meniere disease; however, there are also different clinical and neurophysiological features. In the family, phenotypic variability is present.

Progressive cochleovestibular impairment caused by a point mutation in the COCH gene at DFNA9.

OBJECTIVES: Analysis of phenotype-genotype correlation. STUDY DESIGN: Family study. METHODS: Auditory and vestibulo-ocular functions were examined in a Dutch family with autosomal dominantly inherited sensorineural hearing impairment caused by a 208C > T mutation in the COCH gene, located in chromosome 14q12-q13 (DFNA9). Linear regression analysis of individual longitudinal hearing threshold data (n = 11) on age was performed. RESULTS: Fifteen of the 16 genetically affected persons could be evaluated. They all developed hearing and vestibular impairment symptoms--and in many cases also cardiovascular disease--in the fourth to fifth decade. At the low frequencies (0.25-2 kHz), hearing loss started at the age of about 40 years and showed an average annual progression of approximately 3 dB, finally resulting in profound hearing losses. In two exceptional cases, annual progression attained levels of up to 24 dB. At the high frequencies (4-8 kHz), the average threshold increased from about 50 dB at the age of 35 years to about 120 dB at the age of 75 years (which amounts to 1.8 dB annual threshold increase). All affected individuals tested showed normal ocular motor functions. The patients older than 46 years generally showed absence of the vestibulo-ocular reflex, but their cervico-ocular reflex was enhanced compared with normal subjects, whereas those aged 40 to 46 years showed either severe vestibular hyporeflexia or unilateral caloric areflexia. CONCLUSION: These findings suggest a gradual development of cochleovestibular impairment caused by the new mutation found.

Speech recognition scores related to age and degree of hearing impairment in DFNA2/KCNQ4 and DFNA9/COCH.

OBJECTIVE: To analyze the relationship between pure-tone hearing threshold and speech recognition performance in DFNA2/KCNQ4 and DFNA9/COCH, 2 types of high-frequency nonsyndromic hearing impairment. DESIGN: Case series with cross-sectional analysis of phoneme recognition scores related to age and hearing level. SETTING: University hospital. PATIENTS: Forty-five members of 4 separate families, all carrying 1 of 3 different mutations in the KCNQ4 gene at the DFNA2 locus (1p34); 42 members of 7 separate families, all carrying the same Pro51Ser mutation in the COCH gene at the DFNA9 locus (14q12-q13). RESULTS: The deterioration of speech recognition dropped to a 90% score at a higher level of hearing impairment (pure-tone-average at 1, 2, and 4 kHz) in DFNA2-affected patients (65 dB) than in DFNA9-affected patients (46 dB). CONCLUSION: At similar levels of hearing impairment, DFNA2/KCNQ4-affected patients showed better speech recognition performance than DFNA9/COCH-affected patients.

Non-syndromal autosomal dominant hearing impairment: ongoing phenotypical characterization of genotypes.

This review is concerned with the present state of phenotypical characterization of known genotypes of non-syndromal autosomal dominant hearing impairment. A brief outline of history and context of phenotyping and genotyping of hearing impairment is given with particular reference to the most recent developments in this field, followed by descriptions of DFNA1, DFNA2, DFNA5, DFNA6/14, DFNA8/12, DFNA9, DFNA 13, DFNA17 and DFNA21. Phenotyping those known genotypes may support the ongoing search for mutations in the corresponding gene and enhance genetic counselling. It is recommended that sufficient attention is given to a detailed description of the phenotype in each (newly) described hereditary hearing impairment disorder.

Hereditary cochleovestibular dysfunction due to a COCH gene mutation (DFNA9): a follow-up study of a family.

Cochleovestibular impairment was evaluated, in relation to age, in a longitudinal follow-up study on a Dutch family with a DFNA9 trait caused by a Pro51Ser mutation in the COCH gene on chromosome 14q12-q13. Fourteen cases were genotyped. The onset age of progressive impairment reported by the mutation carriers was between age 35 and 45 years. Pure-tone thresholds deteriorated by about 2-7 dB per year (mean 3.8 dB per year) in a variable, often asymmetrical, fashion. One mutation carrier developed recurrent episodes of vertigo accompanied by nausea and vomiting, resembling Ménière's disease. Two others developed special susceptibility for motion sickness and appeared to have a hyperactive vestibulo-ocular reflex. More advanced stages of vestibular impairment, i.e. vestibular hyporeflexia and complete vestibular areflexia, were eventually found in a number of cases. DFNA9/COCH should be considered as a possible cause in patients developing combined progressive cochlear and vestibular impairment, or suspected hereditary Ménière-like disease, from around middle age.

A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects.

We analysed a Dutch family with autosomal dominant non-syndromic progressive sensorineural hearing loss and mapped the underlying gene defect by genetic linkage analysis to a 11.0 cM region overlapping the DFNA9 interval on chromosome 14q12-q13. Clinically, the Dutch family differs from the original DFNA9 family by a later age at onset and a more clearly established vestibular impairment. A gene that is highly and specifically expressed in the human fetal cochlea and vestibule, COCH (previously described as Coch5B2 ), was mapped to the DFNA9 critical region. Sequence analysis revealed a 208C-->T mutation in the COCH gene, resulting in a Pro51Ser substitution in the predicted protein in all affected individuals of the family but not in unaffected family members and 200 control individuals. The same mutation was also identified in three apparently unrelated families with a similar phenotype, suggesting the presence of a Dutch founder mutation. The function of COCH is unknown but several characteristics of the protein point to a structural role in the extracellular matrix. The mutant serine at position 51 is situated between cysteines and possibly interferes with proper COCH protein folding or its interaction with extracellular matrix proteins.

Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.

Non-syndromic low frequency sensorineural hearing loss (LFSNHL) affecting only 2000 Hz and below is an unusual type of hearing loss that worsens over time without progressing to profound deafness. This type of LFSNHL may be associated with mild tinnitus but is not associated with vertigo. We have previously reported two families with autosomal dominant LFSNHL linked to adjacent but non-overlapping loci on 4p16, DFNA6 and DFNA14. However, further study revealed that an individual with LFSNHL in the DFNA6 family who had a recombination event that excluded the DFNA14 candidate region was actually a phenocopy, and consequently, DFNA6 and DFNA14 are allelic. LFSNHL appears to be genetically nearly homogeneous, as only one LFSNHL family is known to map to a different chromosome (DFNA1). The DFNA6/14 critical region includes WFS1, the gene responsible for Wolfram syndrome, an autosomal recessive disorder characterized by diabetes mellitus and optic atrophy, and often, deafness. Herein we report five different heterozygous missense mutations (T699M, A716T, V779M, L829P, G831D) in the WFS1 gene found in six LFSNHL families. Mutations in WFS1 were identified in all LFSNHL families tested, with A716T arising independently in two families. None of the mutations was found in at least 220 control chromosomes with the exception of V779M, which was identified in 1/336 controls. This frequency is consistent with the prevalence of heterozygous carriers for Wolfram syndrome estimated at 0.3-1%. An increased risk of sensorineural hearing loss has been reported in such carriers. Therefore, we conclude that mutations in WFS1 are a common cause of LFSNHL.