Search Results (83)

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). Targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, the inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference < 10th centile, failed hearing screen, and prematurity. During the first three years of use of this program (2021–2023), 940 (12.3%) of 7651 live-born infants were tested. The most common indication was birthweight < 10th centile (n = 633, 67.3%). Eleven neonates were diagnosed as congenitally infected, for a prevalence of 1.17% (95%CI 0.48–1.86) on tested neonates and of 0.14% (95%CI 0.06–0.23) on live-born infants. None of the cCMV-infected newborns had a failed hearing screen as a testing indication. Implementation of an expanded cCMV screening program appears feasible and of clinical value. Full article

Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by performing perilymph sampling. However, current studies have only focused on the diagnosis of such as otologic conditions. Hearing loss is a feature of certain neuroinflammatory disorders such as multiple sclerosis, and sensorineural hearing loss (SNHL) is widely detected in Alzheimer’s disease. Although the environment of the inner ear is highly regulated, there are several communication pathways between the perilymph of the inner ear and cerebrospinal fluid (CSF). Thus, examination of the perilymph may help understand the mechanism behind the hearing loss observed in certain neuroinflammatory and neurodegenerative diseases. Herein, we review the constituents of CSF and perilymph, the anatomy of the inner ear and its connection with the brain. Then, we discuss the relevance of perilymph sampling in neurology. Currently, perilymph sampling is only performed during surgical procedures, but we hypothesize a simplified and low-invasive technique that could allow sampling in a clinical setting with the same ease as performing an intratympanic injection under direct visual check. The use of this modified technique could allow for perilymph sampling in people with hearing loss and neuroinflammatory/neurodegenerative disorders and clarify the relationship between these conditions; in fact, by measuring the concentration of neuroinflammatory and/or neurodegenerative biomarkers and those typically expressed in the inner ear in aging SNHL, it could be possible to understand if SNHL is caused by aging or neuroinflammation. Full article

Background: Sensory information obtained from the visual, somatosensory, and vestibular systems is responsible for regulating postural control, and if damage occurs in one or more of these sensory systems, postural control may be altered. Objective: To evaluate and compare the postural sway velocity between children with normal hearing and with sensorineural hearing loss (SNHL), matched by sex and age group, and to compare the postural sway velocity between children with normal hearing and with SNHL, with and without vestibular dysfunction. Methods: Cross-sectional study that evaluated 130 children (65 with normal hearing and 65 with SNHL), of both sexes and aged between 7 and 11 years, from public schools of the city of Caruaru, Pernambuco state, Brazil. The postural sway velocity of the center of pressure (COP) was assessed by a force platform, in two directions, anteroposterior (AP) and mediolateral (ML)), in three positions, namely bipedal support with feet together and parallel (parallel feet (PF)), bipedal support with one foot in front of the other (tandem foot (TF)), and single-leg support (one foot (OF)), evaluated with the eyes open and closed. Results: Children with SNHL demonstrated greater postural sway velocity compared to children with normal hearing in all the positions evaluated, with significant differences in the AP direction, with the eyes open (PF: p = 0.001; TF: p = 0.000; OF: p = 0.003) and closed (PF: p = 0.050; TF: p = 0.005). The same occurred in the ML direction, with the eyes open (PF: p = 0.001; TF: p = 0.000; OF: p = 0.001) and closed (PF: p = 0.002; TF: p = 0.000). The same occurred in relation to vestibular function, where the children with SNHL with an associated vestibular dysfunction demonstrated greater postural sway velocity compared to children with normal hearing in all the positions evaluated, demonstrating significant differences in the AP direction, with the eyes open (TF: p = 0.001; OF: p = 0.029) and eyes closed (PF: p = 0.036; TF: p = 0.033). The same occurred in the ML direction, with the eyes open (TF: p = 0.000) and with the eyes closed (PF: p = 0.008; TF: p = 0.009). Conclusions: Children with SNHL demonstrated greater instability of postural control than children with normal hearing in all the directions assessed. Children with SNHL and an associated vestibular dysfunction demonstrated the greatest instability of postural control in this study. Full article

The universal newborn hearing screening (NHS) program was implemented in Russia in 2008 to replace the high-risk newborn hearing screening. More than 95% coverage and significant improvement in early detection and intervention is achieved. Meanwhile, it was shown that current OAE-based hearing screening missed 13% of newborns with genetically ascertained hereditary sensorineural hearing loss (SNHL). The aim of the study is to assess the results of genetic investigation and NHS in a large cohort of Russian children with bilateral SNHL and to study the feasibility of implementation of combined hearing and genetic screening in Russia. Genetic, audiological and NHS data of 1292 pediatric patients with bilateral SNHL born in 2008–2021 were analyzed. GJB2 sequencing was performed for all subjects, 644 patients had pathological GJB2 genotype, 406 of them were homozygous for c.35delG variant. The group of 155 GJB2-negative patients were searched for other SNHL genes, The pathological genotypes were identified at 87 patients. The most frequent genes were STRC (21.8%), USH2A (16.1%), OTOF (8%) and SLC26A4 (6.9%). Children with confirmed genetic etiology passed NHS in 21% of cases. The perspectives of implementation of national comprehensive newborn hearing and genetic screening including whole exome sequencing technologies are discussed. Full article

Executive functions (EFs) are related abilities, associated with the frontal lobes functions, that allow individuals to modify behavioral patterns when they become unsatisfactory. The aim of this study was to assess EFs in children with sensorineural hearing loss (SNHL) and in children with “specific language impairment” (SLI), compared with a control group of children with normal development, to identify specific skill deficits. Three groups of preschool children aged between 2 and 6 years were assessed: 19 children with normal hearing, cognitive, and language development, 10 children with SNHL, and 20 children with SLI. The FE-PS 2-6 Battery was used for the assessment of preschool EFs, supplemented with the Modified Bell Test for the analysis of selective attention. Statistically significant differences were found between the two experimental groups and the control one, regarding the investigated skills. Children with SNHL showed a clear deficit in flexibility, whereas children with SLI had greater problems in self-regulation and management of waiting for gratification. Selective attention was found to be deficient in all three groups, with no statistically significant differences. This study shows that the skills investigated were found to be deficient in both SNHL and SLI patients. It is essential to start targeted exercises based on specific deficient skills as part of the rehabilitation program. It is of great importance to understand the consequences of EF deficit in preschool children to achieve an accurate diagnosis and carry out customized rehabilitation programs. Full article

Background: Sensorineural hearing loss (SNHL) is a multifactorial disorder with potential links to various physiological systems, including the cardiovascular system via blood lipid levels such as triglycerides (TG). This study investigates the causal relationship between TG levels and SNHL using Mendelian randomization (MR), which offers a method to reduce confounding and reverse causality by using genetic variants as instrumental variables. Methods: Utilizing publicly available genome-wide association study (GWAS) data, we performed a two-sample MR analysis. The initial analysis unveiled a causal relationship between TG (GWAS ID: ebi-a-GCST90018975) and SNHL (GWAS ID: finn b-H8_HL_SEN-NAS). Subsequent analysis validated this through MR with a larger sample size for TG (GWAS ID: ieu-b-111) and SNHL. To conduct the MR analysis, we utilized several methods including inverse-variance weighted (IVW), MR Egger, weighted median, and weighted mode. We also employed Cochrane’s Q test to identify any heterogeneity in the MR results. To detect horizontal pleiotropy, we conducted the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test. We performed a leave-one-out analysis to assess the sensitivity of this association. Finally, a meta-analysis of the MR results was undertaken. Results: Our study found a significant positive correlation between TG and SNHL, with OR values of 1.14 (95% CI: 1.07–1.23, p < 0.001) in the IVW analysis and 1.09 (95% CI: 1.03–1.16, p < 0.006) in the replicate analysis. We also found no evidence of horizontal pleiotropy or heterogeneity between the genetic variants (p > 0.05), and a leave-one-out test confirmed the stability and robustness of this association. The meta-analysis combining the initial and replicate analyses showed a significant causal effect with OR values of 1.11 (95% CI: 1.06–1.16, p = 0.01). Conclusion: These findings indicate TG as a risk factor for SNHL, suggesting potential pathways for prevention and intervention in populations at risk. This conclusion underscores the importance of managing TG levels as a strategy to mitigate the risk of developing SNHL. Full article

Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as a promising platform for modeling hearing loss and developing novel therapeutic strategies. SNHL primarily results from the irreversible loss or dysfunction of cochlear mechanosensory hair cells (HCs) and spiral ganglion neurons (SGNs), emphasizing the need for innovative solutions. Current interventions offer symptomatic relief but do not address the root causes. Otic organoids, three-dimensional multicellular constructs that mimic the inner ear’s architecture, have shown immense potential in several critical areas. They enable the testing of gene therapies, drug discovery for sensory cell regeneration, and the study of inner ear development and pathology. Unlike traditional animal models, otic organoids closely replicate human inner ear pathophysiology, making them invaluable for translational research. This review discusses methodological advances in otic organoid generation, emphasizing the use of human pluripotent stem cells (hPSCs) to replicate inner ear development. Cellular and molecular characterization efforts have identified key markers and pathways essential for otic organoid development, shedding light on their potential in modeling inner ear disorders. Technological innovations, such as 3D bioprinting and microfluidics, have further enhanced the fidelity of these models. Despite challenges and limitations, including the need for standardized protocols and ethical considerations, otic organoids offer a transformative approach to understanding and treating auditory dysfunctions. As this field matures, it holds the potential to revolutionize the treatment landscape for hearing and balance disorders, moving us closer to personalized medicine for inner ear conditions. Full article

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice. Full article

Objective: This study aimed to evaluate the effectiveness of endolymphatic duct blockage (EDB) on dizziness control in patients with a large vestibular aqueduct (LVA) and to evaluate its effect on hearing. Study design: This is a prospective nonrandomized study. Setting: Five adults and one child with dizziness and five children with progressive hearing loss were referred to our tertiary centers. Methods: The dizziness handicap inventory (DHI) and DHI-PC (dizziness handicap inventory—patient caregiver) questionnaires were used before and after surgery. All patients underwent a preoperative temporal bone HRCT scan and pure tone audiometry one day before surgery, then four and twelve months after surgery and at the last follow-up. The mean follow-up time was 5.6 years. Student’s t-test was used to compare DHI/-PC results. Results: The DHI scores were 44, 24, 84, 59 and 56 before surgery, respectively, for Patients 1 to 5. The DHI scores at four months was significantly different, i.e., 4, 6, 0, 7 and 18 (p = 0.001). No differences were found between 4 and 12 months. Patient 6 (child) had Trisomy 21; their DHI-PC score dropped from 38 (preoperative score) to 8 (postoperative score), showing no activity limitations; clinical evaluation showed the complete resolution of symptoms. We found no significant differences between hearing loss before the surgery and at 1 and 12 months post operation for four adult patients. Our fifth adult patient’s hearing changed from severe to profound SNHL. For 5 out of 6 pediatric patients, preoperative PTA and mean ABG were 63 dB and 20 dB, respectively; postoperatively, they improved to 42 dB and 16 dB, respectively. The hearing loss level for the sixth pediatric patient dropped from moderate (PTA = 42 dB) to severe (PTA = 85 dB) due to an opening of the endolymphatic sac and a sudden leak of the endolymph. Conclusions: EDB, using two titanium clips, seems to be helpful for controlling vestibular symptoms and for stabilizing hearing or even to improve hearing in 82% of cases. Nevertheless, there is a risk of hearing worsening. Full article

Purpose: To investigate the relationship between glaucoma, pseudoexfoliation and hearing loss (HL). Methods: A systematic literature search following PRISMA guidelines was conducted using the PubMed, Embase, Scopus and Cochrane databases from 1995 up to 28 August 2023. Results: Thirty studies out of the 520 records screened met the inclusion criteria and were included. Most articles (n = 20) analysed the association between pseudoexfoliation syndrome (XFS) and HL, showing XFS patients to have higher prevalence of sensorineural hearing loss (SNHL) at both speech frequencies (0.25, 0.5, 1 and 2 kHz), and higher frequencies (4 and 8 kHz) compared to controls in most cases. No significant differences in prevalence or level of HL between XFS and pseudoexfoliative glaucoma (XFG) were detected in most studies. Eight articles analysed the relationship between primary open-angle glaucoma (POAG) and HL. Overall, a positive association between the two conditions was highlighted across all studies except for two cases. Similarly, articles focusing on NTG and HL (n = 4) showed a positive association in most cases. The role of autoimmunity and, in particular, the presence of antiphosphatidylserine antibodies (APSA) in patients with NTG and HL suggested an underlying autoimmune or vascular mechanism contributing to their pathogenesis. Only one study analysed the relationship between angle-closure glaucoma (ACG) and HL, showing higher incidence of ACG in patients with SNHL compared to normal hearing controls. Conclusions: Most studies detected an association between XFS and HL as well as POAG/NTG/ACG and HL, suggesting the presence of a similar pathophysiology of neurodegeneration. However, given the strength of the association of XFS with HL, it remains unclear whether the presence of XFG is further associated with SNHL. Further research specifically targeted to assess the correlation between glaucoma, XFS and HL is warranted to provide a more comprehensive understanding of this association. Full article

Congenital cytomegalovirus (CMV) infection is the main cause of non-hereditary sensorineural hearing loss (SNHL). In order to shed light on SNHL pathophysiology, we examined the auditory pathway in CMV-infected fetuses; the temporal lobe, in particular the auditory cortex, and the inner ear. We investigated both inner ears and temporal lobes of 20 human CMV-infected fetuses at 21 weeks of gestation. As a negative group, five fetuses from spontaneous miscarriages without CMV infection were studied. Inner ears and temporal lobes were histologically examined, immunohistochemistry for CMV and CMV-PCR were performed. On the auditory cortex, we evaluated the local microglial reaction to the infection. CMV-positive cells were found in 14/20 brains and the damage was classified as severe, moderate, or mild, according to histological features. Fetuses with severe brain damage had a statistically higher temporal lobe viral load and a higher number of activated microglial cells in the auditory cortex compared to fetuses with mild brain damage (p: 0.01; p: 0.01). In the inner ears, the marginal cells of the stria vascularis were the most CMV positive. In our study, CMV affected the auditory pathway, suggesting a tropism for this route. In addition, in the auditory cortex, microglial activation may favor further tissue damage contributing to hearing loss. Full article

Cytomegalovirus (CMV) infections exert a substantial impact on the practice of pediatric infectious diseases. Although most infections in children are minimally symptomatic, several populations are at risk for CMV-associated disease, including immunosuppressed children, children with HIV infection, and, most significantly, children with congenital CMV (cCMV) infection. In spite of the ubiquitous nature of CMV infection, few studies have quantified the impact of CMV-associated care in a pediatric outpatient clinic setting. We evaluated the impact of CMV on clinical care in an outpatient clinic setting over a fifteen-year period at the University of Minnesota (UMN) Masonic Children’s Hospital Pediatric Infectious Diseases (PID) Clinic. A retrospective review of clinic appointments identified 253 unique patients specifically evaluated over this time period for consideration of CMV infection. Of these, 242 were pediatric patients. The majority of the pediatric patients evaluated in the PID clinic were referred for either confirmed or suspected cCMV infection, including children referred for consideration of CMV as a potential reason for a failed newborn hearing screen (NHS) and/or for evaluation of CMV as a possible etiology for documented hearing loss. In total, 116 of the children evaluated during this time period (48%) were unequivocally confirmed as having cCMV infection, with an additional 37 (15%) presenting with presumed, probable, or possible cCMV infection. A total of 16 (7%) of the pediatric CMV cases were confirmed to be post-natally acquired infections. Of the 253 total patients, 11 (4%) of the referrals were for pregnant patients seeking advice about potential therapies in the setting of a known or suspected primary maternal infection during their pregnancies, with an attendant risk of fetal CMV infection. This overview of the demographics and referral patterns for patients evaluated for known or suspected CMV infections in a tertiary care center outpatient PID clinic will serve as a useful baseline assessment, even as future patterns of outpatient care are highly likely to evolve. We predict that PID clinic referrals for newborns identified by universal cCMV screening programs will result in a shift of the CMV outpatient population to healthier infants with clinically inapparent infections, and care will need to be taken by practitioners not to over-medicalize management for these asymptomatic newborns. Full article

GJB2 mutations are the most common cause of autosomal-recessive non-syndromic sensorineural hearing loss (SNHL). The available evidence shows large phenotypic variability across different genotypes and allelic variants. The aim of this study was to investigate the clinical and audiological features of a cohort of subjects with different GJB2/GJB6 gene mutation profiles from a tertiary referral center in Northeastern Italy. We considered 57 patients with GJB2/GJB6 mutations presenting with congenital, non-syndromic SNHL, mainly coming from the Veneto region (Italy). The samples were screened for mutations in exons 1 and 2 of the GJB2 gene and for the GJB6 gene deletion del (GJB6-D13S1830). Free-field and air-conduction frequency-specific thresholds and the pure-tone average (PTA) were considered in the statistical analysis. Five patients (8.87%) had connexin gene mutations in simple heterozygosis, 15 (26.31%) in compound heterozygosis, 34 (59.64%) in homozygosis, and 3 (5.26%) with digenic patterns. The frequency-specific air-conduction thresholds showed significantly different mean values across the different genotypes (Roy’s largest-root test, p = 0.0473). Despite the evidence already available on genetic SNHL, many new insights are to be expected. Further large-scale prospective studies including different populations are necessary to confirm these preliminary findings about the clinical and audiological features of patients with different GJB2/GJB6 gene mutation patterns. Full article

Meniere disease (MD) is a debilitating disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. Severe tinnitus, which occurs in around 1% of patients, is a multiallelic disorder associated with a burden of rare missense single nucleotide variants in synaptic genes. Rare structural variants (SVs) may also contribute to MD and severe tinnitus. In this study, we analyzed exome sequencing data from 310 MD Spanish patients and selected 75 patients with severe tinnitus based on a Tinnitus Handicap Inventory (THI) score > 68. Three rare deletions were identified in two unrelated individuals overlapping the ERBB3 gene in the positions: NC_000012.12:g.56100028_56100172del, NC_000012.12:g.56100243_56101058del, and NC_000012.12:g.56101359_56101526del. Moreover, an ultra-rare large duplication was found covering the AP4M1, COPS6, MCM7, TAF6, MIR106B, MIR25, and MIR93 genes in another two patients in the NC_000007.14:g.100089053_100112257dup region. All the coding genes exhibited expression in brain and inner ear tissues. These results confirm the contribution of large SVs to severe tinnitus in MD and pinpoint new candidate genes to get a better molecular understanding of the disease. Full article

Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in children worldwide. Some regions in the United States and Canada have implemented universal newborn screening for cCMV, which requires molecular diagnostic technologies for identifying cCMV, such as PCR testing of newborn dried blood spots (DBS). This study aimed to evaluate the sensitivity of droplet digital PCR (ddPCR) compared to quantitative real-time PCR to detect CMV DNA in newborn DBS. The limit of detection of various ddPCR primer/probe combinations (singleplex UL55-HEX, singleplex UL83-FAM, and multiplex UL55-HEX/UL83-FAM) was evaluated using the National Institute of Standards and Technology’s (NIST) CMV quantitative standard. Singleplex UL55-HEX ddPCR exhibited the lowest limit of detection among the primer/probe combinations tested for ddPCR. UL55 ddPCR was then compared to real-time PCR in 49 infants with confirmed cCMV identified through newborn screening for CMV in saliva swabs and confirmed by a urine test. The results showed that ddPCR was only positive for 59% (29 out of 49) of the cCMV infants, while real-time PCR was positive for 80% (39 out of 49). Due to its lower sensitivity and throughput, ddPCR may not be suitable for cCMV newborn screening. Full article