Children's Tinnitus Questionnaire - A novel tool for assessing the impact of tinnitus on a child's everyday life.

OBJECTIVE: Self-report instruments are commonly used in tinnitus clinics, but they are presently available only for adults. There is a lack of a validated multi-item instrument to capture tinnitus-related problems in children and their impact on everyday life. This study has developed and validated a specifically child-centered questionnaire to assess the impact of tinnitus. METHODS: Development of the tool consisted of several stages. Following a pilot study on 12 children with tinnitus, a validation study was done on a further 192 children with tinnitus aged between 11 and 14 years. The children had an audiological examination, completed a Visual Analogue Scale (VAS) and the newly framed questionnaire. RESULTS: The development and validation process resulted in the new 11-item Children's Tinnitus Questionnaire (CTQ). It includes items concerning the impact of tinnitus on functional, cognitive, emotional and social domains. The validity of the new tool has been established by finding significant correlations between it and VAS loudness (r = 0.42), VAS annoyance (r = 0.67), and VAS coping (r = -0.41). Validity has also been confirmed by measuring differences in CTQ scores and 4 groups of children having graded incidences of tinnitus. The internal consistency assessed with Cronbach's alpha was high (α = 0.82). CONCLUSION: The Children's Tinnitus Questionnaire (CTQ) is the first fully validated multi-item instrument designed specifically for children. The tool has the potential to become a valuable new instrument for use in clinical practice and research; it might be useful for assessing the impact of tinnitus on those children who find that the condition creates problems in their everyday life.

Accuracy and Repeatability of ChatGPT Based on a Set of Multiple-Choice Questions on Objective Tests of Hearing.

INTRODUCTION: ChatGPT has been tested in many disciplines, but only a few have involved hearing diagnosis and none to physiology or audiology more generally. The consistency of the chatbot's responses to the same question posed multiple times has not been well investigated either. This study aimed to assess the accuracy and repeatability of ChatGPT 3.5 and 4 on test questions concerning objective measures of hearing. Of particular interest was the short-term repeatability of responses which was here tested on four separate days extended over one week. METHODS: We used 30 single-answer, multiple-choice exam questions from a one-year course on objective methods of testing hearing. The questions were posed five times to both ChatGPT 3.5 (the free version) and ChatGPT 4 (the paid version) on each of four days (two days one week and two days the following week). The accuracy of the responses was evaluated in terms of a response key. To evaluate the repeatability of the responses over time, percent agreement and Cohen's Kappa were calculated.  Results: The overall accuracy of ChatGPT 3.5 was 48-49%, while that of ChatGPT 4 was 65-69%. ChatGPT 3.5 consistently failed to pass the threshold of 50% correct responses. Within a single day, the percent agreement was 76-79% for ChatGPT 3.5 and 87-88% for ChatGPT 4 (Cohen's Kappa 0.67-0.71 and 0.81-0.84 respectively). The percent agreement between responses from different days was 75-79% for ChatGPT 3.5 and 85-88% for ChatGPT 4 (Cohen's Kappa 0.65-0.69 and 0.80-0.85 respectively). CONCLUSION: ChatGPT 4 outperforms ChatGPT 3.5 both in accuracy and higher repeatability over time. However, the great variability of the responses casts doubt on possible professional applications of both versions.

Normative values for tests of central auditory processing disorder in children aged from 6 to 12 years old.

INTRODUCTION: Central auditory processing disorders (CAPD) can significantly affect the daily functioning of a child, and the first step in determining whether rehabilitation procedures are required is a proper diagnosis. Different guidelines for making diagnoses have been published in the literature, and in various centers normative values for psychoacoustic tests of CAPD have been used internally. The material presented in this paper is based on more than 1000 children and is the largest collection so far published. The aim of this study is to present normative values for tests assessing CAPD in children aged 6 to 12 years, divided by age at last birthday. METHOD: We tested 1037 children aged 6 to 12 years who were attending primary schools and kindergartens. The criteria for inclusion were a normal audiogram, intellectually normal, no developmental problems, and no difficulties in auditory processing. To evaluate auditory processing all children were given three tests on the Senses Examination Platform: the Frequency Pattern Test (FPT), Duration Pattern Test (DPT), and Dichotic Digit Test (DDT). RESULTS: The results from 1,037 children allowed us to determine normative values for FPT, DPT, and DDT in seven different age groups (6 through to 12 years). We developed a newapproach, based on quantile-based norms, to determine normative values in each group. Three categories - average, below-average, and above-average - allow for a broader but more realistic interpretation than those used previously. We compare our results with published standards. CONCLUSIONS: Our study is the largest normative database published to date for CAPD testing, setting a standard for each child by age in years. We used the Senses Examination Platform, a universal tool, to unify standards for the classification of CAPD. Our study can serve as a basis for the development of a Polish model for the diagnosis of CAPD.

Vocal fold electromyography in patients with endoscopic features of unilateral laryngeal paralysis.

<b><br>Introduction:</b> Electromyography (EMG) of the larynx provides information on the electrophysiological condition of laryngeal muscles and innervation. Integration of information obtained from the EMG exams with the clinical parameters as obtained by other methods for laryngeal assessment (endoscopy, perceptual and acoustic analysis, voice self-assessment) provides a multidimensional picture of dysphonia, which is of particular importance in patients with vocal fold (VF) mobility disorders accompanied by glottic insufficiency.</br> <b><br>Aim:</b> The aim of this study was to evaluate laryngeal EMG records acquired in subjects with unilateral vocal fold immobilization with signs of atrophy and glottic insufficiency.</br> <b><br>Material and methods:</b> From the available material of 74 EMG records of patients referred for the exam due to unilateral laryngeal paralysis, records of 17 patients with endoscopic features suggestive of complete laryngeal muscle denervation were selected. The EMG study of thyroarytenoid muscles of mobile and immobile VFs was evaluated qualitatively and quantitatively at rest and during volitional activity involving free phonation of vowel /e/ [ε].</br> <b><br>Results:</b> In all patients, the EMG records from mobile VFs were significantly different from those from immobile VFs. Despite endoscopic features of paralysis, no VF activity whatsoever was observed in as few as 2 patients so as to meet the neurophysiological definition of paralysis. In 88% of cases, electromyographic activity of the thyroarytenoid muscle was observed despite immobilization and atrophy of the vocal fold. In these patients, neurogenic type of record was observed with numerous high- -amplitude mobility units. On the basis of the results, quantitative features of EMG records indicative of paralysis and residual activity of the thyroarytenoid muscle were determined.</br> <b><br>Conclusions:</b> Qualitative and quantitative analysis of laryngeal EMG records provides detailed information on the condition of vocal fold muscles and innervation. EMG records of mobile vs immobile VFs differ significantly from each other. Endoscopic evaluation does not provide sufficient basis for the diagnosis of complete laryngeal muscle denervation.</br>.

Holistic assessment of cochlear implant outcomes using the international classification of functioning disability and health model: data analysis of a longitudinal prospective multicenter study.

PURPOSE: To study outcome after cochlear implantation using the Cochlear Implant (CI) outcome assessment protocol based on the International Classification of Functioning, Disability and Health (ICF) model (CI-ICF). METHODS: Raw data of a prospective, longitudinal, multicenter study was analyzed. Seventy-two CI candidates were assessed preoperatively and six months postoperatively using the CI-ICF protocol. Following tools were used: (1) Work Rehabilitation Questionnaire (WORQ), (2) Abbreviated Profile of Hearing Aid Benefit (APHAB), (3) Audio Processor Satisfaction Questionnaire (APSQ), (4) Speech, Spatial, and Qualities of Hearing Scale (SSQ12), (5) Hearing Implant Sound Quality Index (HISQUI19), (6) Nijmegen CI Questionnaire (NCIQ) (7) pure tone audiometry, (8) speech audiometry, (9) sound localization. RESULTS: There was a significant improvement of speech discrimination in quiet (p = 0.015; p < 0.001) and in noise (p = 0.041; p < 0.001), sound detection (p < 0.001), tinnitus (p = 0.026), listening (p < 0.001), communicating with-receiving-spoken messages (p < 0.001), conversation (p < 0.001), family relationships (p < 0.001), community life (p = 0.019), NCIQ total score and all subdomain scores (p < 0.001). Subjective sound localization significantly improved (p < 0.001), while psychometric sound localization did not. There was no significant subjective deterioration of vestibular functioning and no substantial change in sound aversiveness. CI users reported a high level of implant satisfaction postoperatively. CONCLUSION: This study highlights the positive impact of cochlear implantation on auditory performance, communication, and subjective well-being. The CI-ICF protocol provides a holistic and comprehensive view of the evolution of CI outcomes.

Effect of the COVID-19 Pandemic on Resting-State Brain Activity in Individuals with Tinnitus.

This study looked at the possible effect of the COVID-19 pandemic on individuals who came to our clinic seeking relief from tinnitus. The performance of the subjects during the COVID-19 pandemic was compared with similar individuals who came to our clinic before the pandemic began. The study involved 50 adults with chronic tinnitus, made up of a study group (24 subjects tested during the COVID-19 pandemic of 2020-2021) and a control group before the pandemic began (26 subjects tested from 2013 to 2017). None of the 24 reported having contracted COVID-19. Data collection involved the Tinnitus Handicap Inventory (THI) questionnaire, audiological tests, and quantitative electroencephalography (qEEG). In terms of THI scores, there were no statistically significant differences between the two groups. However, with regard to qEEG, some changes were observed, with significant decreases in alpha and beta band activity in the study group compared to the control group, particularly over the auditory cortex. We conclude that COVID-19 did not have a discernible impact on the general well-being of individuals with tinnitus. However, it did appear to alter brain activity, specifically in the alpha and beta bands over the auditory cortex, and these reults warrant further investigation.

Effectiveness of transcutaneous vagus nerve stimulation for the treatment of tinnitus: an interventional prospective controlled study.

OBJECTIVES: The aim of this interventional non-randomised prospective controlled study was to assess the effectiveness of transcutaneous vagus nerve stimulation (tVNS) in human subjects with tinnitus. DESIGN: The ParasymTM tVNS device was paired with an auditory stimulation. Treatment and observations were conducted over 12 weeks. Audiological evaluation was performed. Responses from a set of questionnaires and quantitative electroencephalography (qEEG) before and after treatment were collected. Voice measurements were done to assess possible side-effects of tVNS. STUDY SAMPLE: The study involved 29 adults who had chronic tinnitus (15 patients who underwent tVNS paired with sounds and a control group of 14 patients who did not). RESULTS: In general, subjective and objective measurements of tinnitus showed no improvement in the study group compared to the controls, although certain parameters as gauged by the questionnaires did statistically improve. The loudness and frequency of tinnitus remained the same in both groups. For the qEEG, activity in the theta band increased significantly in the study group compared to the control group. CONCLUSIONS: The tVNS was not effective in reducing tinnitus symptoms in our study group. However, changes in the theta band suggest there might be cortical effects that might, with sustained treatment, lead to improvements.

A Good Practice Guide for Organizing the Scientific Program of International Conferences.

This paper provides a step-by-step guide for organizing the scientific program (OSP) of international conferences. Through informal discussions, a panel of experts organizing international conferences came up with this guide, which includes a flowchart, checklist, and detailed discussions of each step. Subsequently, additional specialists were invited to evaluate this synopsis and provide their input. All of the participants approved the final version after the outline was improved. This guide proposes the following six steps: 1) preparation, 2) recruitment, 3) building the agenda, 4) cross-checking the program, 5) reviewing and finalizing, and 6) in-conference refining. Thirteen items are specified across the six main steps in a detailed checklist. This OSP guide includes a flowchart and a checklist for providing a comprehensive manual for establishing, conducting, and organizing international scientific conferences. Understanding the procedures that are expected to be followed when holding a scientific conference enables the involved parties to organize and assign tasks to one another as well as create a schedule that allows them to finish their work on time. This guide can be used at any kind of scientific conference to describe an organized process, resulting in a professional and distinguished scientific program.

A Case Report of Riboflavin Treatment and Cochlear Implants in a 4-Year-Old Girl with Progressive Hearing Loss and Delayed Speech Development: Brown-Vialetto-Van Laere Syndrome.

BACKGROUND Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a motor neuron disorder of childhood, which can be associated with sensorineural deafness. This report describes a 4-year-old Polish girl with progressive hearing loss and delayed speech development diagnosed with Brown-Vialetto-Van Laere syndrome who was treated with riboflavin (vitamin B2) and cochlear implants. CASE REPORT The case report concerns a girl from Poland who, at the age of 2 years 10 months, developed progressive atypical neurological symptoms of unknown etiology: ataxia of the upper and lower limbs, gait abnormalities, generalized muscle weakness, visual and hearing problems, and regression of speech development. A karyotype study (whole-exome sequencing) revealed alterations within SLC52A2, leading to the diagnosis of Brown-Vialetto-Van Laere syndrome and initiation of high-dose riboflavin treatment. As a 4-year-old child, she presented to the Institute of Physiology and Pathology of Hearing - World Hearing Center in Poland with progressive hearing loss and speech regression. Hearing tests revealed bilateral profound sensorineural hearing loss with auditory neuropathy. Surgical treatment was applied in the form of bilateral cochlear implantation. CONCLUSIONS This report shows the importance of genetic testing in infants who present with atypical symptoms or signs. In this case, the diagnosis of Brown-Vialetto-Van Laere syndrome resulted in timely correction of the genetic riboflavin (vitamin B2) deficiency and improved hearing following the use of cochlear implants.

Hyperacusis Assessment Questionnaire-A New Tool Assessing Hyperacusis in Subjects with Tinnitus.

Hyperacusis, a kind of decreased sound tolerance, is difficult to measure objectively. It often co-occurs with tinnitus. There is a need for valid and reliable patient-reported outcome measures to capture this subjective phenomenon. The aim of the study was to create a questionnaire capturing hyperacusis in terms of loudness, fear, and pain and to evaluate its psychometric properties. The study sample consisted of 106 adult patients with hyperacusis and tinnitus with a mean age of 45.2 years. A medical interview, an audiological examination, and several questionnaires (the Tinnitus Handicap Inventory, the Hyperacusis Questionnaire, the State-Trait Anxiety Inventory, and Visual Analog Scales) were applied. The final 14-item Hyperacusis Assessment Questionnaire showed an appropriate three-factor structure with 70.5% of the variance explained. Convergent and divergent validity were confirmed by correlations with other measures of hyperacusis, anxiety, tinnitus severity, misophonia, and hearing thresholds. The internal consistency assessed with Cronbach's alpha was excellent (α = 0.91), as was reproducibility (intraclass correlation, ICC = 0.96). The new Hyperacusis Assessment Questionnaire is a psychometrically sound and brief tool assessing the severity of hyperacusis in terms of loudness, fear, and pain. It can be used in clinical practice and scientific research for patients with hyperacusis and tinnitus.

Satisfaction with life in a sample of prelingually deaf cochlear implant users with a good command of spoken Polish as the primary language.

INTRODUCTION: This study investigated the level of satisfaction with life (SWL) in a group of cochlear implant (CI) users who had been prelingually deaf but were orally educated. They had received one or two CIs (as a child, adolescent, or adult) and were highly competent Polish speakers. This study looked at three factors that may affect SWL - psychosocial, deafness/hearing and communication related, and sociodemographic. METHODS: The participants were prelingually deaf CI users who had learned highly competent spoken Polish as their primary language. They had been educated in mainstream or integrated schools (not schools for the deaf), and had no other disability or severe illness. Measurements were done with 5 questionnaires: the Satisfaction With Life Scale (SWLS), the I-Others Questionnaire, the Patient Health Questionnaire (PHQ-9), the Deaf Identity Development Scale (DIDS), and the Nijmegen Cochlear Implant Questionnaire (NCIQ). RESULTS: The SWL level of the group was similar to that of the standard Polish population. SWL was positively related to positive self-perception, acceptance of oneself as a deaf person, and to perceiving the benefits of having a CI (as measured by three NCIQ domains: self-esteem, activity limitations, and social interactions). On the other hand, negative self-perception, marginal deaf identity, and depressive symptoms were negatively related to SWL. There was no relationship between SWL and knowledge of sign language. Lower depressive symptoms and greater hearing loss were both significant predictors of SWL, although those who used two CIs generally had a lower SWL. CONCLUSIONS: Prelingually deaf CI users with low SWL require psychological support in many spheres, including working through problems of deaf identity, self-acceptance, and depression. Additional research should involve diverse DHH CI users, including those with limited spoken Polish competency or sign language skills, as well as members of the Polish Deaf community.

Hyperbaric oxygen therapy as an adjunct to corticosteroid treatment in sudden sensorineural hearing loss: a retrospective study.

Background: A retrospective clinical study was conducted to test the impact of including hyperbaric oxygen therapy in the treatment of patients with sudden sensorineural hearing loss (SSNHL). Materials and methods: A total of 63 adult patients with sudden sensorineural hearing loss diagnosed between 2015 and 2023 were divided into two groups: 36 patients treated with intratympanic glucocorticoid and orally administered glucocorticoid who also underwent hyperbaric oxygen therapy and 27 patients treated with intratympanic glucocorticoid and prolonged orally administered glucocorticoid (without hyperbaric oxygen therapy). An audiological evaluation was performed using pure-tone audiometry. Results: Average hearing gain as measured by pure tone average was 12.5 dB HL (+/- 19.9 dB HL) in the patients treated with steroids combined with HBOT, and was 14.1 dB HL (+/- 17.9 dB) in the patients treated with steroids alone. Successful treatment (complete recovery or marked improvement) was observed in 27.8% of the patients in the first group and in 25.5% in the second group. There was no statistically significant difference between the groups. Conclusion: Both groups of patients-those treated with glucocorticoids and those treated with glucocorticoids and HBOT-had similar hearing outcomes. A prospective, controlled, and randomized study would provide more reliable knowledge about the efficacy of HBOT in treating SSNHL.

Outcomes of Cochlear Implantation Using FLEX26 Electrode: Audiological Results and Quality of Life after 12 Months.

INTRODUCTION: The electrode length is one of the many factors impacted on results of cochlear implantation. Among lateral wall flexible electrode arrays the latest one is FLEX26 (MED-EL GmbH, Innsbruck, Austria). The main aim of the study was to evaluate the preservation of residual hearing, the level of speech understanding, and quality of life after cochlear implantation with FLEX26 electrode array. METHODS: The study was conducted in a tertiary referral centre. Fifty-two patients implanted unilaterally with FLEX26, including 10 EAS patients (electric acoustic stimulation) and 42 ES patients (electric stimulation). The intervention was minimally invasive cochlear implantation via the round window. Pure-tone audiometry (0.125-8 kHz) was performed preoperatively and at 1, 6, and 12 months postoperatively. Twelve-month hearing preservation was established using HEARRING group formula. Quality of life was measured with AQoL-8D (Assessment of Quality of Life-8 Dimensions) pre- and postoperatively. RESULTS: Residual hearing was preserved in 88.8% EAS patients. Quality of life was significantly better postoperatively in comparison to preoperative period (the effect size for overall quality of life was 0.49). Especially, it increased in relationships and senses dimensions (the effect sizes 0.47 and 0.44, respectively). CONCLUSION: Preservation of residual hearing can be achieved in the majority of patients implanted with FLEX26. Improvement of quality of life was also documented. FLEX26 seems to be an option for surgeons who seek an electrode providing sufficient cochlear coverage.

Can an individual with low frequency hearing in the candidate ear benefit from a cochlear implant even if they have normal hearing in the other ear?

PURPOSE: To determine hearing preservation and subjective benefit after cochlear implant (CI) surgery in patients with low frequency hearing in the ear to be implanted (i.e., they have partial deafness, PD) and close to normal hearing in the other. METHODS: There were two study groups. The test group was made up of 12 adult patients (mean age 43.4 years; SD 13.6) with normal hearing or mild hearing loss in one ear, and with PD in the ear to be implanted. The reference group consisted of 12 adult patients (mean age 44.5 years; SD 14.1) who had PD in both ears and who underwent unilateral implantation in their worse ear. Hearing preservation was assessed 1 and 14 months after CI surgery using the Skarzynski Hearing Preservation Classification System. The APHAB questionnaire was used to evaluate the benefit from the CI. RESULTS: The differences in HP% between the groups were not significant: mean hearing preservation (HP%) in the test group was 82% one month after CI surgery and 75% some 14 months after implantation; corresponding results in the reference group were 71% and 69%. However, on the APHAB background noise subscale, the benefit in the test group was significantly larger than in the reference group. CONCLUSION: To a large extent it was possible to preserve low-frequency hearing in the implanted ear. This means that individuals with low frequency hearing in the implanted ear (partial deafness) and with normal hearing in the other generally received more benefits from cochlear implantation than did patients with partial deafness in both ears. We conclude that residual low frequency hearing in the ear to be implanted should not be considered a contraindication for a CI in a patient with single-sided deafness.

Differential item functioning of the tinnitus handicap inventory across gender groups and subjects with or without hearing loss.

OBJECTIVES: Tinnitus is a phantom sound sensation without an external sound source. Due to its subjective and multifaceted nature it is measured using multi-item self-reported instruments. Many well-validated tinnitus-related questionnaires are available for clinical practice and scientific research, but so far no attention has been paid to their measurement invariance. The study aimed to examine measurement invariance of the Tinnitus Handicap Inventory with regard to gender and hearing impairment, and to identify the items that show differential item functioning (DIF) across the groups. DESIGN: This is a retrospective study using medical data from patients with tinnitus. They completed the Tinnitus Handicap Inventory (THI) and underwent pure-tone audiometry. STUDY SAMPLE: 1106 adult patients with tinnitus (554 women and 552 men; 320 with normal hearing and 786 with hearing loss), aged 19-84 years. RESULTS: In the analysis, multi-group confirmatory factor analysis, hybrid ordinal logistic regression, Kernel smoothing in Item Response Theory, and lasso regression were applied. Measurement invariance was demonstrated across gender, but across hearing status the measurement was non-invariant. Five items were found to have DIF. CONCLUSIONS: Researchers and clinicians should be aware of the potential risk of response bias when tinnitus severity is evaluated.

Validation of the Polish Version of Voice Handicap Index-10.

PURPOSE: The aim of this study was to adapt and evaluate the psychometric properties of the Polish version of the VHI-10. METHODS: We enrolled 183 subjects-118 patients with voice disorders and 65 without voice disorders. RESULTS: All items were correlated with each other and were strongly correlated with the total score (rho ≥ 0.70), the only exception being item five (rho = 0.56). Internal consistency was very high, with Cronbach's alpha = 0.92. There was a statistically significant difference between patients with voice disorders and healthy controls in terms of VHI-10 global score (U = 251.0; P < 0.001). There was a statistically significant negative correlation between mean phonation time (MPT) and VHI-10 (rho = -0.30; P < 0.01). Only the amplitude perturbation quotient (APQ) was correlated positively with the global score (rho = 0.22; P = 0.020). There were statistically significant and positive correlations between VHI-10 scores and GRBAS evaluation. Correlations between global scores of VHI-30 and VHI-10, and between VHI-30 subscales and the corresponding items from VHI-10, were very strong (respectively 0.97 and 0.89-0.94). In the patient group, there was high test-retest reproducibility (intraclass correlation = 0.91). A cut-off value of 8.5 points was estimated. CONCLUSION: The Polish version of VHI-10 showed excellent internal consistency, good test-retest reproducibility, and had clinical validity. It is a useful brief tool for self-reported evaluation and reliable assessment of patients with voice disorders.

Magnitude of medial olivocochlear reflex assayed by tone-burst-evoked otoacoustic emissions: reliability and comparison with click-evoked emissions.

OBJECTIVE: The purpose of this pilot study was to evaluate the magnitude of the medial olivocochlear reflex (MOCR) estimated by the reduction in tone-burst evoked otoacoustic emissions (TBOAEs) measured at three levels and at three frequencies in response to fixed contralateral white noise. Results were compared with commonly used click-evoked otoacoustic emissions (CEOAEs). DESIGN: TBOAEs and CEOAEs, with and without contralateral 60 dB SPL white noise, were measured in response to stimulation at 55, 65, and 75 dB peSPL. In each subject, the set of measurements was performed twice. Of particular interest were the MOCR and its repeatability. STUDY SAMPLE: 15 normally hearing persons (13 women, average age 32.3 years, SD = 8.1). RESULTS: For both CEOAE and TBOAEs, the reliability of the MOCR was much better for broadband measurements than for half-octave-band filtered estimates. At the same time, the reliability of MOCR in half-octave bands was higher for TBOAEs than for CEOAEs, especially at 2 and 4 kHz. CONCLUSIONS: For general applications where broadband MOCR is of interest, the highest magnitude and reliability is provided by CEOAEs. However, TBOAEs may be better if a particular frequency band is of interest.

MMP-9 plasma level as biomarker of cochlear implantation outcome in cohort study of deaf children.

PURPOSE: If before cochlear implantation it was possible to assay biomarkers of neuroplasticity, we might be able to identify those children with congenital deafness who, later on, were at risk of poor speech and language rehabilitation outcomes. METHODS: A group of 40 children aged up to 2 years with DFNB1-related congenital deafness was observed in this prospective cohort study over three follow-up intervals (0, 8, and 18 months) after cochlear implant (CI) activation. Children were assessed for auditory development using the LittlEARS Questionnaire (LEAQ) score, and at the same time, measurements were made of matrix metalloproteinase-9 (MMP-9) plasma levels. RESULTS: There were significant negative correlations between plasma levels of MMP-9 at 8-month follow-up and LEAQ score at cochlear implantation (p = 0.04) and LEAQ score at 18-month follow-up (p = 0.02) and between MMP-9 plasma levels at 18-month follow-up and LEAQ score at cochlear implantation (p = 0.04). As already reported, we confirmed a significant negative correlation between MMP-9 plasma level at cochlear implantation and LEAQ score at 18-month follow-up (p = 0.005). Based on this latter correlation, two clusters of good and poor CI performers could be isolated. CONCLUSIONS: The study shows that children born deaf who have an MMP-9 plasma level of less than 150 ng/ml at cochlear implantation have a good chance of attaining a high LEAQ score after 18 months of speech and language rehabilitation. This indicates that MMP-9 plasma level at cochlear implantation is a good prognostic marker for CI outcome.

Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss.

BACKGROUND: Low-frequency non-syndromic hearing loss (LFNSHL) is a rare form of hearing loss (HL). It is defined as HL at low frequencies (≤2,000 Hz) resulting in a characteristic ascending audiogram. LFNSHL is usually diagnosed postlingually and is progressive, leading to HL affecting other frequencies as well. Sometimes it occurs with tinnitus. Around half of the diagnosed prelingual HL cases have a genetic cause and it is usually inherited in an autosomal recessive mode. Postlingual HL caused by genetic changes generally has an autosomal dominant pattern of inheritance and its incidence remains unknown. SUMMARY: To date, only a handful of genes have been found as causing LFNSHL: well-established WFS1 and, reported in some cases, DIAPH1, MYO7A, TNC, and CCDC50 (respectively, responsible for DFNA6/14/38, DFNA1, DFNA11, DFNA56, and DFNA44). In this review, we set out audiological phenotypes, causative genetic changes, and molecular mechanisms leading to the development of LFNSHL. KEY MESSAGES: LFNSHL is most commonly caused by pathogenic variants in the WFS1 gene, but it is also important to consider changes in other HL genes, which may result in similar audiological phenotype.

The Genetic Background of Hearing Loss in Patients with EVA and Cochlear Malformation.

The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic SLC26A4 variants are considered the major cause of inner ear malformation but the genetics still needs clarification. The aim of this study was to identify the cause of EVA in patients with hearing loss (HL). Genomic DNA was isolated from HL patients with radiologically confirmed bilateral EVA (n = 23) and analyzed by next generation sequencing using a custom HL gene panel encompassing 237 HL-related genes or a clinical exome. The presence and segregation of selected variants and the CEVA haplotype (in the 5' region of SLC26A4) was verified by Sanger sequencing. Minigene assay was used to evaluate the impact of novel synonymous variant on splicing. Genetic testing identified the cause of EVA in 17/23 individuals (74%). Two pathogenic variants in the SLC26A4 gene were identified as the cause of EVA in 8 of them (35%), and a CEVA haplotype was regarded as the cause of EVA in 6 of 7 patients (86%) who carried only one SLC26A4 genetic variant. In two individuals with a phenotype matching branchio-oto-renal (BOR) spectrum disorder, cochlear hypoplasia resulted from EYA1 pathogenic variants. In one patient, a novel variant in CHD7 was detected. Our study shows that SLC26A4, together with the CEVA haplotype, accounts for more than half of EVA cases. Syndromic forms of HL should also be considered in patients with EVA. We conclude that to better understand inner ear development and the pathogenesis of its malformations, there is a need to look for pathogenic variants in noncoding regions of known HL genes or to link them with novel candidate HL genes.