Objectives: We examined which preoperative diagnostic measure is most suited to serve as a selection criterion to determine adult cochlear implantation (CI) candidacy. Design: Preoperative... Show moreObjectives: We examined which preoperative diagnostic measure is most suited to serve as a selection criterion to determine adult cochlear implantation (CI) candidacy. Design: Preoperative diagnostic measures included pure tone audiometry (PTA; 0.5, 1, 2, 4 kHz), speech perception tests (SPT) unaided with headphones and with best-aided hearing aids (in quiet and in noise). Gain in speech perception was used as outcome measure. Performance of preoperative measures was analysed using the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Study sample: This retrospective longitudinal cohort study included 552 post-lingually deafened adults with CI in a tertiary referral centre in the Netherlands. Results: Best-aided SPT in quiet was the most accurate in defining which CI candidates improved their speech perception in quiet postoperatively. For an improvement in speech perception in noise, the best-aided SPT in noise was the most accurate in defining which adult would benefit from CI. PTA measures performed lower compared to the SPT measures. Conclusions: SPT is better than PTA for selecting CI candidates who will benefit in terms of speech perception. Best-aided SPT in noise was the most accurate for indicating an improvement of speech perception in noise but was only evaluated in high performers with residual hearing. These insights will assist in formulating more effective selection criteria for CI. Show less
ObjectivesWe examined which preoperative diagnostic measure is most suited to serve as a selection criterion to determine adult cochlear implantation (CI) candidacy.DesignPreoperative diagnostic... Show moreObjectivesWe examined which preoperative diagnostic measure is most suited to serve as a selection criterion to determine adult cochlear implantation (CI) candidacy.DesignPreoperative diagnostic measures included pure tone audiometry (PTA; 0.5, 1, 2, 4 kHz), speech perception tests (SPT) unaided with headphones and with best-aided hearing aids (in quiet and in noise). Gain in speech perception was used as outcome measure. Performance of preoperative measures was analysed using the area under the curve (AUC) of receiver operating characteristic (ROC) curves.Study sampleThis retrospective longitudinal cohort study included 552 post-lingually deafened adults with CI in a tertiary referral centre in the Netherlands.ResultsBest-aided SPT in quiet was the most accurate in defining which CI candidates improved their speech perception in quiet postoperatively. For an improvement in speech perception in noise, the best-aided SPT in noise was the most accurate in defining which adult would benefit from CI. PTA measures performed lower compared to the SPT measures.ConclusionsSPT is better than PTA for selecting CI candidates who will benefit in terms of speech perception. Best-aided SPT in noise was the most accurate for indicating an improvement of speech perception in noise but was only evaluated in high performers with residual hearing. These insights will assist in formulating more effective selection criteria for CI. Show less
Numerous studies have shown the recovery of auditory function in mouse models of genetic hearing loss following AAV gene therapy, yet translation to the clinic has not yet been demonstrated. One... Show moreNumerous studies have shown the recovery of auditory function in mouse models of genetic hearing loss following AAV gene therapy, yet translation to the clinic has not yet been demonstrated. One limitation has been the lack of human inner ear cell lines or tissues for validating viral gene therapies. Cultured human inner ear tissue could help confirm viral tropism and efficacy for driving exogenous gene expression in targeted cell types, establish promoter efficacy and perhaps selectivity for targeted cells, confirm the expression of therapeutic constructs and the subcellular localization of therapeutic proteins, and address the potential cellular toxicity of vectors or exogenous constructs. To begin to address these questions, we developed an explant culture method using native human inner ear tissue excised at either fetal or adult stages. Inner ear sensory epithelia were cultured for four days and exposed to vectors encoding enhanced green fluorescent protein (eGFP). We focused on the synthetic AAV9-PHP.B capsid, which has been demonstrated to be efficient for driving eGFP expression in the sensory hair cells of mouse and non-human primate inner ears. We report that AAV9-PHP.B also drives eGFP expression in fetal cochlear hair cells and in fetal and adult vestibular hair cells in explants of human inner ear sensory epithelia, which suggests that both the experimental paradigm and the viral capsid may be valuable for translation to clinical application. Show less
This study investigated the phenotypic spectrum of PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract) syndrome caused by biallelic variants in the ABHD12... Show moreThis study investigated the phenotypic spectrum of PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract) syndrome caused by biallelic variants in the ABHD12 gene. A total of 15 patients from 12 different families were included, with a mean age of 36.7 years (standard deviation [SD] +/- 11.0; range from 17.5 to 53.9) at the most recent examination. The presence and onset of neurological, audiological and ophthalmic symptoms were variable, with no evident order of symptom appearance. The mean best-corrected visual acuity was 1.1 logMAR (SD +/- 0.9; range from 0.1 to 2.8; equivalent to 20/250 Snellen) and showed a trend of progressive decline. Different types of cataract were observed in 13 out of 15 patients (87%), which also included congenital forms of cataract. Fundus examination revealed macular involvement in all patients, ranging from alterations of the retinal pigment epithelium to macular atrophy. Intraretinal spicular hyperpigmentation was observed in 7 out of 15 patients (47%). From an ophthalmic perspective, clinical manifestations in patients with PHARC demonstrate variability with regard to their onset and severity. Given the variable nature of PHARC, an early multidisciplinary assessment is recommended to assess disease severity. Show less
Background and Introduction:Vestibular schwannomas (VSs) are the most common tumors of the cerebellopontine angle, typically presenting unilaterally with ipsilateral sensorineural hearing loss ... Show moreBackground and Introduction:Vestibular schwannomas (VSs) are the most common tumors of the cerebellopontine angle, typically presenting unilaterally with ipsilateral sensorineural hearing loss (SNHL). The mechanism of tumor-induced hearing loss has recently been shown to be related to secreted tumor factors, in addition to mechanical compression of the adjacent auditory nerve, and these factors may percolate through CSF or blood to affect contralateral hearing as well. Methods:This is a retrospective study of medical records for patients treated for VS at Mass Eye and Ear from January 1994 through October 2018. Included patients had unilateral VS and sequential audiometry allowing for longitudinal assessment of hearing over time. Mass Eye and Ear's audiology database was used to select age- and sex-matched case controls, also with sequential audiometry, from the non-VS population. Subgroup analysis was performed by age, sex, baseline hearing, and tumor size at initial diagnosis. Hearing loss progression was performed using Kaplan-Meier analysis to account for variable follow-up times. Results:A total of 661 patients were identified with VS and sequential audiometry. The population was predominantly female vs. male (368 vs. 293,p= 0.0035), driven primarily by younger patients with Koos 4 tumors (76 female vs. 49 male,p= 0.016). Patients with normal baseline hearing bilaterally (N= 241) demonstrated no significant difference in hearing loss progression in VS-contralateral vs. control ears. Patients with abnormal baseline VS-ipsilateral hearing (N= 190), however, demonstrated significantly higher likelihood of reaching moderate SNHL in VS-contralateral ears. Subgroup analysis by age, sex, and baseline tumor size did not yield any subgroup-specific trends for hearing loss progression. Discussion and Conclusion:This is the largest study to date tracking long-term bilateral hearing outcomes in patients with VS, and demonstrates that, in patients with abnormal hearing in the VS-ipsilateral ear, there exists a long-term risk of progression to moderate hearing loss in the contralateral ear as well. Combined with the absence of significant changes in word understanding in the affected ears, these findings may provide clues to the nature of tumor-secreted factors involved in VS-associated hearing loss. Female predominance within the VS patient population is confirmed, driven mostly by younger female patients with Koos 4 tumors. Show less
This study examined the quantity and quality of parental linguistic input to toddlers with moderate hearing loss (MHL) compared with toddlers with normal hearing (NH). The linguistic input to... Show moreThis study examined the quantity and quality of parental linguistic input to toddlers with moderate hearing loss (MHL) compared with toddlers with normal hearing (NH). The linguistic input to eighteen toddlers with MHL and twenty-four toddlers with NH was examined during a 10-minute free-play activity in their home environment. Results showed that toddlers with MHL were exposed to an equivalent amount of parental linguistic input compared to toddlers with NH. However, parents of toddlers with MHL used less high-level facilitative language techniques, used less mental state language, and used shorter utterances than parents of toddlers with NH. Quantity and quality measures of parental linguistic input were positively related to the expressive language abilities of toddlers with MHL. Show less
This study examined the quantity and quality of parental linguistic input to toddlers with moderate hearing loss (MHL) compared with toddlers with normal hearing (NH). The linguistic input to... Show moreThis study examined the quantity and quality of parental linguistic input to toddlers with moderate hearing loss (MHL) compared with toddlers with normal hearing (NH). The linguistic input to eighteen toddlers with MHL and twenty-four toddlers with NH was examined during a 10-minute free-play activity in their home environment. Results showed that toddlers with MHL were exposed to an equivalent amount of parental linguistic input compared to toddlers with NH. However, parents of toddlers with MHL used less high-level facilitative language techniques, used less mental state language, and used shorter utterances than parents of toddlers with NH. Quantity and quality measures of parental linguistic input were positively related to the expressive language abilities of toddlers with MHL. Show less
Broekhof, E.; Kouwenberg, M.; Oosterveld, P.; Frijns, J.H.M.; Rieffe, C. 2020
No assessment tools are available to measure shame and guilt in children who are deaf or hard of hearing (DHH), while these self-conscious emotions might play a role in the frequently noted social... Show moreNo assessment tools are available to measure shame and guilt in children who are deaf or hard of hearing (DHH), while these self-conscious emotions might play a role in the frequently noted social and behavioral problems in this group. Therefore, the aim of this study was to validate the Brief Shame and Guilt Questionnaire (BSGQ) in DHH children. In addition, we examined associations of shame and guilt with social anxiety, self-esteem, delinquency, and psychopathic behaviors. A sum of 225 hearing (M-age = 11.62 years) and 108 DHH (M-age = 11.82 years) participants completed the self-report BSGQ. Multigroup confirmatory factor analysis confirmed the two-factor structure (i.e., shame and guilt) of the BSGQ in the DHH group. Measurement invariance was established across both groups. However, the DHH group reported lower levels of self-conscious emotions in comparison with the hearing group. The BSGQ showed good concurrent validity, where shame was associated with higher levels of social anxiety and lower levels of self-esteem, and guilt was associated with lower levels of delinquency and psychopathic behavior in both groups. Future research should investigate the potential behavioral consequences of lower reported levels of self-conscious emotions in DHH youth. Show less
Schrauwen, I.; Valgaeren, H.; Tomas-Roca, L.; Sommen, M.; Altunoglu, U.; Wesdorp, M.; ... ; Bokhoven, H. van 2019
Purpose: To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP) family and otosclerosis.Methods: We performed exome sequencing in a four-generation family... Show morePurpose: To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP) family and otosclerosis.Methods: We performed exome sequencing in a four-generation family presenting nonprogressive HCFP and mixed hearing loss (HL). MEPE was analyzed using either Sanger sequencing or molecular inversion probes combined with massive parallel sequencing in 89 otosclerosis families, 1604 unrelated affected subjects, and 1538 unscreened controls.Results: Exome sequencing in the HCFP family led to the identification of a rare segregating heterozygous frameshift variant p.(Gln425Lysfs*38) in MEPE. As the HL phenotype in this family resembled otosclerosis, we performed variant burden and variance components analyses in a large otosclerosis cohort and demonstrated that nonsense and frameshift MEPE variants were significantly enriched in affected subjects (p = 0.0006-0.0060).Conclusion: MEPE exerts its function in bone homeostasis by two domains, an RGD and an acidic serine aspartate-rich MEPE-associated (ASARM) motif inhibiting respectively bone resorption and mineralization. All variants associated with otosclerosis are predicted to result in nonsense mediated decay or an ASARM-and-RGD-truncated MEPE. The HCFP variant is predicted to produce an ASARM-truncated MEPE with an intact RGD motif. This difference in effect on the protein corresponds with the presumed pathophysiology of both diseases, and provides a plausible molecular explanation for the distinct phenotypic outcome. Show less
Clemens, E.; Vries, A.C.H. de; Zehnhoff-Dinnesen, A.A.; Tissing, W.J.E.; Loonen, J.J.; Pluijm, S.F.M.; ... ; Heuvel-Eibrink, M.M. van den 2017
Objectives/HypothesisThe purpose of this study was to determine whether concomitant chemoradiation (CCRT)-induced hearing loss is progressive over time or not.Study DesignLong-term (LT) follow-up... Show moreObjectives/HypothesisThe purpose of this study was to determine whether concomitant chemoradiation (CCRT)-induced hearing loss is progressive over time or not.Study DesignLong-term (LT) follow-up study.MethodsBetween 1999 and 2004, 158 patients with head and neck cancer were treated with intravenous (IV) CCRT (n=80) or intraarterial CCRT (n=78). Audiometry was performed before, short-term (ST), and LT posttreatment. Differences in hearing were assessed with a multivariable linear regression analysis, incorporating the effect of aging.ResultsLong-term audiometry (median 4.5 years) was available in 67 patients (42%). At ST follow-up, a deterioration of 21.6 decibel was seen compared to baseline at pure-tone averages (PTA) 8-10-12.5 kHz. At LT follow-up, this deterioration further increased with 5 decibel (P = 0.005). Only in CCRT-IV patients was a significant progressive treatment-induced hearing loss seen, at PTA 8-10-12.5 kHz (P = 0.005), PTA 1-2-4 kHz air conduction (P = 0.014), and PTA 0.5-1-2 kHz bone conduction (P = 0.045).ConclusionCCRT-induced hearing impairment was progressive over time, especially in higher frequencies and only in CCRT-IV patients, with a modest deterioration of 5 decibel 4.5 years post-treatment.Level of Evidence4. Laryngoscope, 124:2720-2725, 2014 Show less
Theunissen, E.A.R.; Dreschler, W.A.; Latenstein, M.N.; Rasch, C.R.N.; Baan, S. van der; Boer, J.P. de; ... ; Zuur, C.L. 2014
Objective: This study aimed to propose an ototoxicity grading system sensitive to the effect of ototoxicity on specific daily life situations like speech intelligibility and the perception of ultra... Show moreObjective: This study aimed to propose an ototoxicity grading system sensitive to the effect of ototoxicity on specific daily life situations like speech intelligibility and the perception of ultra-high sounds and to test its feasibility compared to current criteria.Methods: Pure tone averages (PTAs) for speech perception (1-2-4 kHz) and ultra-high frequencies (8-10-12.5 kHz) were incorporated. Threshold shift and hearing level posttreatment were taken into account. Criteria were tested on head and neck cancer patients treated with (chemo-)radiotherapy ([C]RT) and compared with the Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) and the American Speech-Language-Hearing Association criteria (ASHA).Results: Grades 1 and 2 were based on threshold shifts from baseline (in dB) and subjective complaints. Grades 3 and 4 were defined as treatment-induced hearing loss of 35 dB at PTA 1-2-4 kHz and >= 70 dB at PTA 1-2-4 kHz, respectively. In high-dose cisplatin CRT incidences by the new criteria, CTCAEv4 and ASHA were comparable (78%-88%). In RT and low-dose cisplatin CRT, incidences were 36% to 39% in the new criteria versus 22% to 53% in CTCAEv4 and ASHA.Conclusion: The new criteria show an increased sensitivity to ototoxicity compared to CTCAEv4 and ASHA and provide insight into the effect of hearing loss on certain daily life situations. The new grading system seems feasible for clinic and research purposes. Show less
Theunissen, S.C.P.M.; Rieffe, C.; Kouwenberg, M.; Raeve, L. de; Soede, W.; Briaire, J.J.; Frijns, J.H.M. 2012
Background: High rates of psychopathology were found amongst deaf adolescents, but little is known about the psychosocial risk factors. This study investigated whether (1) less severe deafness and... Show moreBackground: High rates of psychopathology were found amongst deaf adolescents, but little is known about the psychosocial risk factors. This study investigated whether (1) less severe deafness and/or acquired or otherwise complicated deafness, and (2) having mainly contacts with hearing people, each represent chronic stressful conditions that moderate the associations between self-esteem and emotional problems. In addition, the moderating effect of observed peer rejection on the association between social acceptance and behavioural problems was explored. Method: Deaf adolescents of normal intelligence (N= 68) completed the Self Perception Profile for Adolescents. Psychopathology was assessed using a semi-structured interview with adolescents and reports by parents, teachers and expert ratings. Data on moderator variables were collected from school records, parental and teachers’ reports. Results: Emotional mental health problems were negatively associated with self-esteem and positivelywith peer rejection. The association between self-esteem and emotional problems was moderated by the deafness variable less severe deafness or acquired or otherwise complicated deafness. Behavioural mental health problems were positively associated with social acceptance and peer rejection but negatively with the amount of involvement with hearing people. Peer rejection moderated the association between social acceptance and behavioural problems. Conclusions: The findings emphasise the importance of considering se Show less
