Search Results (434)

Background: Meniere’s disease is characterized by a triad of vertigo episodes, fluctuating hearing loss, and tinnitus. The disease is followed by a loss of quality of life in patients, with the severity depending on the individual and the stage of the disease. Since there are no quantitatively validated tests that connect all elements of the disease, the only source of subjective data that can be analyzed is the disease diary and questionnaires, among which the MDPOSI (Meniere’s Disease Patient-Oriented Symptom-Severity Index) stands out as a designated quality-of-life assessment tool. This study aims to evaluate the differences in the questionnaire depending on the clinical characteristics of the disease. Methods: The study recruited 60 patients, with clinical variables including age, gender, disease laterality, caloric testing results, and PTA results, the presence of spontaneous nystagmus, pathological values of calorimetric testing, or rotatory chair testing abnormalities. Results: The appearance of spontaneous nystagmus showed a significant association with worse hearing threshold values at 500 Hz (p = 0.036, OR 4.416) and higher. Worse SRT scores correlated with Q1 (p = 0.011), Q2 (p = 0.028), Q4 (p = 0.045), Q5 (p = 0.013), and the total MDPOSI score (p = 0.008, 0.339). Multivariate analysis showed that a higher total value of the MDPOSI questionnaire was statistically significantly associated with older age (p = 0.042) and spontaneous nystagmus (p = 0.037). Conclusions: There is a correlation between the clinical characteristics of Meniere’s disease and the MDPOSI questionnaire, making it useful for assessing quality of life and disease progression. Full article

Pathogenic variants in the MAP1B gene have been associated with neurological impairment, including intellectual disability, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, brain malformations, cognitive hearing loss, short stature, and dysmorphic features. However, few cases with detailed clinical characterization have been reported. We describe a 12-year-old boy carrying a loss-of-function MAP1B variant, presenting with severe elimination disorders despite normal intelligence. He was referred to the genetics service due to persistent elimination issues, including daytime urinary incontinence, nocturnal enuresis, and fecal incontinence. He had normal motor and cognitive development, with an IQ of 99; however, he also presented with ADHD, short stature, microcephaly, and myopia. Brain MRI revealed bilaterial subependymal periventricular nodular heterotopia (PVNH). Audiometry showed normal bilateral hearing. Testing fragile X syndrome (FXS) and karyotype analyses yielded normal results. Whole exome sequencing (WES) revealed a nonsense pathogenic variant in MAP1B (c.895 C>T; p.Arg299*). No other family members showed a similar phenotype; however, a great-uncle and a great-aunt had a history of nocturnal enuresis until age 10. The patient’s deceased mother had short stature and psychiatric disorders, and a history of consanguinity was reported on the maternal side. This case broadens the phenotypic spectrum associated with MAP1B syndrome, suggesting that elimination disorder, frequently reported in FXS, should also be evaluated in MAP1B pathogenic variant carriers. In addition, the presence of short stature also appears to be part of the syndrome. Full article

Background/Objectives: Cochlear “injury” is thought to be a significant cause of tinnitus in patients with hearing loss. Interestingly, individuals with normal hearing may also experience tinnitus. This study evaluates otoacoustic distortion product emissions (DPOAEs) in individuals with normal hearing who experience tinnitus perception. Methods: In this prospective study, the tinnitus group (TG) consisted of 34 subjects with tinnitus (four unilaterally) and normal hearing (threshold ≤ 25 dBHL at 0.25–8 kHz). The control group (CG) comprised 10 healthy volunteers (20 ears) without tinnitus and normal hearing. Medical history was recorded, and all participants underwent a complete otolaryngological examination, pure tone audiometry, and DPOAE recording (DP-gram, L1 = 55 dB, L2 = 65 dB, for F2: 619–10,000 Hz). Moreover, participants in the TG completed a detailed tinnitus history (with self-rated loudness scoring) and the Tinnitus Handicap Inventory (Greek-version THI-G) and underwent tinnitus analysis. Results: The recorded mean DPOAE values during the DP-gram of the CG were significantly larger in amplitude at low (t-test, Bonferroni-corrected p < 0.09) and high frequencies (t-test, Bonferroni-corrected p < 0.02) compared with the TG. Tinnitus assessment showed tinnitus pitch matching at the frequency area in the DP-gram, where the acceptance recording criteria were not met. There were no statistically significant differences in tinnitus onset, self-rated loudness scores of >70, and severe disability (THI-G > 58) for TG subjects in whom DPOAEs were not recorded at frequencies of ≤1000 Hz. Participants with abnormal DPOAEs at around 4000 Hz had tinnitus of sudden onset and severe disability (THI-G > 58). Finally, those with pathological recordings of DPOAEs at ≥6000 Hz had gradual onset tinnitus (Pearson Chi-square test, p < 0.05). Conclusions: DPOAEs in normal hearing individuals with tinnitus show lower amplitudes in low and high frequencies compared with normal hearing individuals without tinnitus. The tinnitus matched-frequency coincided with the frequency area where DPOAEs were abnormal. Full article

Background: Sudden-onset bilateral mixed hearing loss in adults is an extremely rare condition but challenging to diagnose and treat. Conductive hearing loss is associated with otitis media, while the simultaneous presence of a sensorineural component requires supplementary investigation for possible shared pathophysiological mechanisms. Case Presentation: We report the case of a 41-year-old male who was admitted to our hospital with a 48 h history of bilateral, fast progressive hearing loss following a viral illness. The audiologic testing revealed bilateral severe mixed hearing loss. Tympanometry indicated the presence of middle-ear effusion, and myringotomy confirmed the existence of pressurized serous fluid. Treatment consisted of systemic and intratympanic corticosteroids, antibiotics, and supportive therapy. The patient had an unexpected full recovery of auditory function within one month. Discussion: Multiple hypotheses were considered. We hypothesized the coexistence of unrelated conductive and sensorineural hearing loss or a unifying pathological process. Theories discussed include a direct viral insult to the cochlear structures or even pressure-mediated damage to the basal cochlea due to the simultaneous inward displacement of the oval and round windows. The complete resolution of hearing loss is the indicator of a reversible etiology, possibly due to transient inner ear dysfunction secondary to middle-ear pathology or viral infection. Conclusions: This case illustrates the complexity of diagnosing acute mixed hearing loss. This report emphasizes a rare case of sudden-onset bilateral mixed hearing loss with a complete recovery, contributing valuable insight into under-reported and diagnostically complex presentations. Full article

Background: Cochlear implantation is widely used to provide auditory rehabilitation to individuals with severe-to-profound sensorineural hearing loss. However, electrode insertion during cochlear implantation leads to inner ear trauma, damage to sensory structures, and consequently, loss of residual hearing. There is very limited information regarding the target proteins involved in electrode insertion trauma (EIT) following cochlear implantation. Methods: The aim of our study was to identify target proteins and host molecular pathways involved in cochlear damage following EIT utilizing the iTRAQ™ (isobaric tags for relative and absolute quantification) technique using our ex vivo model. The organ of Corti (OC) explants were dissected from postnatal day 3 rats and subjected to EIT or left untreated (control). The proteins were extracted, labelled, and subjected to ultra-high performance liquid chromatography–tandem mass spectrometry. Results: We identified distinct molecular pathways involved in EIT-induced cochlear damage. Confocal microscopy confirmed the expression of these identified proteins in OC explants subjected to EIT. By separating the apical, middle, and basal cochlear turns, we deciphered a topographic array of host molecular pathways that extend from the base to the apex of the cochlea, which are activated post-trauma following cochlear implantation. Conclusions: The identification of target proteins involved in cochlear damage will provide novel therapeutic targets for the development of effective treatment modalities for the preservation of residual hearing in implanted individuals. Full article

Transmembrane protein 43 (TMEM43 or LUMA) encodes a highly conserved protein found in the nuclear and endoplasmic reticulum membranes of many cell types and the intercalated discs and adherens junctions of cardiac myocytes. TMEM43 is involved in facilitating intra/extracellular signal transduction to the nucleus via the linker of the nucleoskeleton and cytoskeleton complex. Genetic mutations may result in reduced TMEM43 expression and altered TMEM43 protein cellular localization, resulting in impaired cell polarization, intracellular force transmission, and cell–cell connections. The p.S358L mutation causes arrhythmogenic right ventricular cardiomyopathy type-5 and is associated with increased absorption of lipids, fatty acids, and cholesterol in the mouse small intestine, which may promote fibro-fatty replacement of cardiac myocytes. Mutations (p.E85K and p.I91V) have been identified in patients with Emery–Dreifuss Muscular Dystrophy-related myopathies. Other mutations also lead to auditory neuropathy spectrum disorder-associated hearing loss and have a negative association with cancer progression and tumor cell survival. This review explores the pathogenesis of TMEM43 mutation-associated diseases in humans, highlighting animal and in vitro studies that describe the molecular details of disease processes and clinical, histologic, and molecular manifestations. Additionally, we discuss TMEM43 expression-related conditions and how each disease may progress to severe and life-threatening states. Full article

Aminoglycoside antibiotics are critical in clinical use for treating severe infections, but they can occasionally cause irreversible sensorineural hearing loss. To establish a rational pathway for otoprotectant discovery, we provide an integrated, three-tier methodology—comprising cell-model selection, transcriptomic analysis, and a gentamicin–Texas Red (GTTR) uptake assay—to guide the development of otoprotective strategies. We first utilized two murine auditory cell lines—UB/OC-2 and HEI-OC1. We focused on TMC1 and OCT2 and further explored the underlying mechanisms of ototoxicity. UB/OC-2 exhibited a higher sensitivity to gentamicin, which correlated with elevated OCT2 expression confirmed via RT-PCR and Western blot. Transcriptomic analysis revealed upregulation of PI3K-Akt, calcium, and GPCR-related stress pathways in gentamicin-treated HEI-OC1 cells. Protein-level analysis further confirmed that gentamicin suppressed phosphorylated Akt while upregulating ER stress markers (GRP78, CHOP) and apoptotic proteins (cleaved caspase 3, PARP). Co-treatment with PI3K inhibitors (LY294002, wortmannin) further suppressed Akt phosphorylation, supporting the role of PI3K-Akt signaling in auditory cells. To visualize drug entry, we used GTTR to evaluate its applicability as a fluorescence-based uptake assay in these cell lines, which were previously employed mainly in cochlear explants. Sodium thiosulfate (STS) and N-acetylcysteine (NAC) significantly decreased GTTR uptake, suggesting a protective effect against gentamicin-induced hair cell damage. In conclusion, our findings showed a complex ototoxic cascade involving OCT2- and TMC1-mediated drug uptake, calcium imbalance, ER stress, and disruption of PI3K-Akt survival signaling. We believe that UB/OC-2 cells serve as a practical in vitro model for mechanistic investigations and screening of otoprotective compounds. Additionally, GTTR may be a simple, effective method for evaluating protective interventions in auditory cell lines. Overall, this study provides molecular-level insights into aminoglycoside-induced ototoxicity and introduces a platform for protective strategies. Full article

Background/Objectives: Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. In cases of severe-to-profound SNHL, cochlear implantation (CI) is a widely used intervention, but outcomes remain variable due to possible neurodevelopmental comorbidities. This study aimed to evaluate the long-term auditory and language outcomes in children with cCMV after CI and to explore clinical and radiological predictors of post-CI performance. Methods: Fifty-three children with cCMV and bilateral severe-to-profound SNHL who underwent CI at five tertiary referral centers in Italy were included in the study. Auditory and language outcomes were assessed pre- and post-implantation using the Categories of Auditory Performance II (CAP-II) scale, the Nottingham 3-Level Classification, and the Bates Language Development Scale. Brain MRI abnormalities were classified according to the Alarcón classification. Correlations were explored between outcome scores and symptomatic status at birth, MRI findings, and neurodevelopmental comorbidities. Results: At birth, 40 children (75.5%) were symptomatic and 13 (24.5%) asymptomatic. Neurodevelopmental comorbidities were present in 19 children (35.8%). MRI was normal in 15 (28.3%), mildly abnormal in 26 (49%), and moderately to severely abnormal in 12 (22.6%). Auditory and language outcomes improved significantly post-CI (p < 0.001), though the outcomes varied widely. Twenty-five children (47%) reached CAP level ≥ 6, and thirteen (23%) reached Bates Level 6. Symptomatic status at birth correlated weakly with worse CAP (ρ = −0.291, p = 0.038) and Bates (ρ = −0.310, p = 0.028) scores. Higher Alarcón scores were significantly associated with neurodevelopmental comorbidities, though not directly with post-CI auditory and language outcomes. Finally, the presence of neurodevelopmental disabilities was generally associated with lower results, even if without statistical significance. Conclusions: CI provides substantial auditory and language benefit in children with cCMV, even in cases of severe neurodevelopmental comorbidities. MRI and developmental assessments, as well as perinatal history for clinical signs and symptoms, are helpful in guiding expectations and personalizing post-implantation support. Full article

Background: Syndromic inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders, involving the retina and additional organs. Over 80 forms of syndromic IRD have been described. Methods: We aimed to phenotypically and genotypically characterize a cohort of 171 individuals from 140 Israeli families with syndromic IRD. Ophthalmic examination included best corrected visual acuity, fundus examination, visual field testing, retinal imaging and electrophysiological evaluation. Most participants were also evaluated by specialists in fields relevant to their extra-retinal symptoms. Genetic analyses included haplotype analysis, homozygosity mapping, Sanger sequencing and next-generation sequencing. Results: In total, 51% of the families in the cohort were consanguineous. The largest ethnic group was Muslim Arabs. The most common phenotype was Usher syndrome (USH). The most common causative gene was USH2A. In 29% of the families, genetic analysis led to a revised or modified clinical diagnosis. This included confirmation of an atypical USH diagnosis for individuals with late-onset retinitis pigmentosa (RP) and/or hearing loss (HL); diagnosis of Heimler syndrome in individuals with biallelic pathogenic variants in PEX6 and an original diagnosis of USH or nonsyndromic RP; and diagnosis of a mild form of Leber congenital amaurosis with early-onset deafness (LCAEOD) in an individual with a heterozygous pathogenic variant in TUBB4B and an original diagnosis of USH. Novel genotype–phenotype correlations included biallelic pathogenic variants in KATNIP, previously associated with Joubert syndrome (JBTS), in an individual who presented with kidney disease and IRD, but no other features of JBTS. Conclusions: Syndromic IRDs are a highly heterogeneous group of disorders. The rarity of some of these syndromes on one hand, and the co-occurrence of several syndromic and nonsyndromic conditions in some individuals, on the other hand, complicates the diagnostic process. Genetic analysis is the ultimate way to obtain an accurate clinical diagnosis in these individuals. Full article

Introduction: This study aimed to compare different scoring methods, such as phoneme, syllable, and word-based scoring, during word recognition in noise testing and their interaction with hearing loss severity. These scoring methods provided a structured framework for refining clinical audiological diagnosis by revealing underlying auditory processing at multiple linguistic levels. We highlight how scoring differences inform differential diagnosis and guide targeted audiological interventions. Methods: Pure tone audiometry and word-in-noise testing were conducted on 100 subjects with a wide range of hearing loss severity. Speech recognition was scored using phoneme, syllable, and word-based methods. All procedures were designed to reflect standard diagnostic protocols in clinical audiology. Discriminant function analysis examined how these scoring methods differentiate the degree of hearing loss. Results: Results showed that each method provides unique information about auditory processing. Phoneme-based scoring has pointed out basic auditory discrimination; syllable-based scoring can capture temporal and phonological processing, while word-based scoring reflects real-world listening conditions by incorporating contextual knowledge. These findings emphasize the diagnostic value of each scoring approach in clinical settings, aiding differential diagnosis and treatment planning. Conclusions: This study showed the effect of different scoring methods on hearing loss differentiation concerning severity. We recommend the integration of phoneme-based scoring into standard diagnostic batteries to enhance early detection and personalize rehabilitation strategies. Future research must involve studies about integration with other speech perception tests and applicability across different clinical settings. Full article

Background/Objectives: The vestibulo-respiratory reflex regulates the tension of the respiratory muscles, which prevents apneas and awakenings during sleep. This study aimed to determine whether functional deficits in the inner ear disturb sleep quality. Methods: We compared sleep parameters in patients with their first episode of acute inner ear deficit (Group A: sudden idiopathic vertigo attack, sudden sensorineural hearing loss), chronic functional inner ear impairment (Group B: chronic peripheral vertigo, permanent hearing loss), and in healthy individuals (Group C). Polygraphy recordings were performed twice, in Group A at the onset of acute otoneurological symptoms and the second time after their withdrawal with an interval of 1 to 13 days, in Group B after 1 to 6 days, and in Group C after 1 to 8 days. Results: In Group A during the symptomatic night, overall and central apnea-hypopnea indices were significantly higher and snoring time was longer. Group A also had higher central apnea-hypopnea index on the first night compared to healthy individuals. In chronic disorders, sleep recordings showed lower autonomic arousal index than in controls or symptomatic nights in Group A. Conclusions: These findings highlight the severity of sleep apnea indicators in Group A. Our results suggest that acute dysfunction of the inner ear substantially impacts central neuronal signaling responsible for regulating normal sleep-related breathing and leads to a deterioration in sleep quality in contrast to individuals with chronic inner ear impairments. It can also be assumed that people with chronic vertigo or hearing loss experience less interrupted sleep than healthy individuals. Full article

Background: Wolfram syndrome (WFS), also known as DIDMOAD, is a rare monogenic neurodegenerative disorder characterized by four key components: non-autoimmune insulin-dependent diabetes mellitus (DM), optic atrophy, sensorineural hearing loss, and diabetes insipidus. Although it significantly affects quality of life, gonadal dysfunction, particularly hypogonadism, remains underrecognized. Methods: In total, 45 patients (25 men, 20 women) with genetically confirmed WFS from a single tertiary-care center were prospectively followed to assess gonadal function. Men underwent hormonal evaluations, semen analysis, imaging tests, and testicular biopsies. In women, data on age at menarche, menstrual irregularities, and age at menopause were recorded. Hormonal analyses, including anti-Müllerian hormone (AMH) levels, and imaging tests were also conducted. Results: Hypogonadism was identified in 19 men (76.0%), of whom 17 (68.0%) had hypergonadotropic hypogonadism and 2 (8.0%) had hypogonadotropic hypogonadism. Testicular biopsies showed seminiferous tubule damage, Sertoli cell predominance, and reduced Leydig cells. Azoospermia was observed in 12 patients, whereas others presented with oligozoospermia, teratozoospermia, or asthenozoospermia. Most patients exhibited low testosterone levels along with elevated LH and FSH, suggesting primary testicular failure, except for two cases of hypogonadotropic hypogonadism. Correlations between biomarkers, onset age and severity have been analyzed and provide important insights regarding medical treatment. In women, menstrual irregularities were universal, with 20% experiencing premature menopause. Four patients had low AMH levels, with ovarian atrophy in three and a postmenopausal uterus in two, indicating early hypogonadism risk. Conclusions: Gonadal dysfunction is a significant yet overlooked feature of WFS, requiring systematic evaluation during puberty and beyond. Proper management is essential to mitigate metabolic disturbances and psychological impacts, including infertility distress, relationship challenges, and quality of life concerns. Addressing sexual health is crucial as WFS patients live longer and aspire to establish relationships or start families. Full article

Disorders of vesicular trafficking and genetic defects in autophagy play a critical role in the development of metabolic and neurometabolic diseases. These processes govern intracellular transport and lysosomal degradation, thereby maintaining cellular homeostasis. In this article, we present two siblings with a novel homozygous variant in VPS51 (Vacuolar protein sorting 51) gene (c.1511C>T; p.Thr504Met), exhibiting developmental delay, a thin corpus callosum, severe intellectual disability, epilepsy, microcephaly, hearing loss, and dysphagia. This study aimed to investigate the effects of the novel VPS51 gene variation at the RNA and protein level in fibroblasts derived from patients. A comparative proteomic analysis, which has not been previously elucidated, was performed to identify uncharacterized proteins associated with vesicular trafficking. Furthermore, the impact of disrupted pathways on mitochondria–lysosome contact sites was assessed, offering a thorough pathophysiological evaluation of GARP/EARP (Golgi Associated Retrograde Protein / Endosome Associated Retrograde Protein) complex dysfunction. An analysis of mRNA expression indicated decreased levels of the VPS51 gene, alongside modifications in the expression of autophagy-related genes (LC3B, p62, RAB7A, TBC1D15). Western blotting demonstrated a reduction in VPS51 and autophagy-related protein levels. Proteomic profiling revealed 585 differentially expressed proteins, indicating disruptions in vesicular trafficking, lysosomal function, and mitochondrial metabolism. Proteins involved in mitochondrial β-oxidation and oxidative phosphorylation exhibited downregulation, whereas pathways related to glycolysis and lipid synthesis showed upregulation. Live-cell confocal microscopy revealed a notable increase in mitochondria–lysosome contact sites in patient fibroblasts, suggesting that VPS51 protein dysfunction contributes to impaired organelle communication. The findings indicate that the novel VPS51 gene variation influences intracellular transport, autophagy, and metabolic pathways, offering new insights into its involvement in neurometabolic disorders. Full article

Background/Objectives: Rehabilitation success with a cochlear implant (CI) varies considerably and identifying predictive factors for the reliable prediction of speech understanding with CI remains a challenge. Hoppe and colleagues have recently described a predictive model, which was specifically based on Cochlear™ recipients with a four-frequency pure tone average (4FPTA) ≤ 80 dB HL. The aim of this retrospective study is to test the applicability to an independent patient cohort with extended inclusion criteria. Methods: The Hoppe et al. model was applied to CI recipients with varying degrees of hearing loss. Model performance was analyzed for Cochlear™ recipients with 4FPTA ≤ 80 dB HL and for all recipients regardless of 4FPTA. Subgroup analyses were conducted by WRS_max and CI manufacturer. Results: The model yielded comparable results in our patient cohort when the original inclusion criteria were met (n = 24). Extending the model to patients with profound hearing loss (4FPTA > 80 dB HL; n = 238) resulted in a weaker but significant correlation (r = 0.273; p < 0.0001) between predicted and measured word recognition score at 65 dB with CI (WRS₆₅(CI)). Also, a higher percentage of data points deviated by more than 20 pp, either better or worse. When patients provided with CIs from different manufacturers were enrolled, the prediction error was also higher than in the original cohort. In Cochlear™ recipients with a maximum word recognition score (WRS_max) > 0% (n = 83), we found a moderate correlation between measured and predicted scores (r = 0.3274; p = 0.0025). Conclusions: In conclusion, as long as the same inclusion criteria are used, the Hoppe et al. (2021) prediction model results in similar prediction success in our cohort, and thus seems applicable independently of the cohort used. Nevertheless, it has limitations when applied to a broader and more diverse patient cohort. Our data suggest that the model would benefit from adaptations for broader clinical use, as the model lacks sufficient sensitivity in identifying poor performers. Full article

Background/Objectives: This study examined the effect of sound preference on loudness tolerance (LTLs) and preferred listening levels (PLLs) using personal listening devices (PLDs). The implication of this relationship on hearing health promotion counseling and practices using PLDs is discussed. Methods: Participants were 50 individuals, aged 21 to 90 years, with normal hearing or hearing loss. Listeners rated several sound samples (i.e., music, running speech, and machinery noise) played through a PLD using earphones according to their sound preference (i.e., enjoyable, acceptable, and unpleasant) and then self-adjusted the volume setting to their LTL and PLL for a sound sample in each sound preference category. Results: Most listeners judged music (70%) as enjoyable, running speech (54%) as acceptable, and machinery noise (84%) as unpleasant. No significant differences were found in LTLs according to sound preference, but PLLs for enjoyable sounds occurred at significantly higher levels compared with those deemed acceptable or unpleasant. Conclusions: Listeners using PLDs perceived LTLs and PLLs differently according to their sound preferences. PLLs occurred at significantly higher volumes for sounds deemed enjoyable when using PLDs. The implication is that hearing health counseling should include information to PLD users on the potential of altered loudness perception with enjoyable sounds, which may lead to higher and riskier PLD listening levels. Full article