Research progress on incomplete partition type 3 inner ear malformation.

PURPOSE: This review aims to provides a comprehensive overview of the latest research progress on IP-III inner ear malformation, focusing on its geneticbasis, imaging features, cochlear implantation, and outcome. METHODS: Review the literature on clinical and genetic mechanisms associated with IP-III. RESULTS: Mutations in the POU3F4 gene emerge as the principal pathogenic contributors to IP-III anomalies, primarily manifesting through inner ear potential irregularities leading to deafness. While cochlear implantation stands as the primary intervention for restoring hearing, the unique nature of the inner ear anomaly escalates the complexity of surgical procedures and postoperative results. Hence, meticulous preoperative assessment to ascertain surgical feasibility and postoperative verification of electrode placement are imperative. Additionally, gene therapy holds promise as a prospective treatment modality. CONCLUSIONS: IP-III denotes X-linked recessive hereditary deafness, with cochlear implantation currently serving as the predominant therapeutic approach. Clinicians are tasked with preoperative assement and individualized postoperative rehabilitation.

Imaging in children with hearing loss. / Bildgebende Diagnostik bei Schwerhörigkeit im Kindesalter.

BACKGROUND: Since the introduction of hearing screening in Germany in 2009, pediatric hearing disorders are detected at an early stage. Early therapy is essential for language development. Imaging plays a central role in diagnosis and therapy planning. METHOD: Imaging findings of the most relevant causes of pediatric hearing disorders are presented. Specific attention is given to the method used in each case - CT or MRI. RESULTS AND CONCLUSIONS: While CT is the method of choice for conductive hearing loss, a combination of CT and MRI with high-resolution T2-3D sequences has been established as the best diagnostic method for sensorineural hearing loss. The most common causes of conductive hearing loss in childhood are chronic inflammation and cholesteatoma. Congenital malformations of the outer or middle ear are less frequent. In the case of sensorineural hearing loss, the cause is located in the inner ear and/or the cochlear nerve or the cerebrum. In these cases, congenital malformations are the most common cause. KEY POINTS: · CT and MRI are necessary to identify morphological causes of hearing disorders and to clarify the possibility of hearing-improving ear surgery or cochlear implantation.. · Contraindications for surgical procedures must be excluded.. · Anatomical variants that may be risk factors for surgery must be described.. CITATION FORMAT: · Sorge I, Hirsch F, Fuchs M et al. Imaging diagnostics for childhood hearing loss. Fortschr Röntgenstr 2023; 195: 896 - 904.

Postnatal genetic umbilical cord analysis for earliest possible detection of inherited hearing impairment.

INTRODUCTION: The most common sensorineural disorder in humans is hearing impairment and approximately 60% of prelingual hearing disorders are genetic. Especially parents with a congenital deaf child want to know as early as possible whether their second born child has the same genetic defect or not. The aim of this study is to demonstrate that postnatal genetic umbilical cord analysis is both the earliest detection possibility and sufficient. METHODS: We included first born children with severe hearing impairment that underwent cochlear implantation. All included patients were analyzed genetically and exhibited mutations of either DFNB1 loci or SLC26A4 gene. Additionally, the umbilical cord of the sibling underwent genetic analysis to detect hereditary genetic mutations as early as possible. RESULTS: 49 newborn children out of 22 families were included in this study. Genetic analysis revealed clinical relevant mutations in all first born children and in four siblings via umbilical cord analysis. All patients who have been diagnosed with a relevant genetic mutation that caused severe hearing impairment underwent hearing rehabilitation via cochlear implant surgery. CONCLUSION: This study demonstrates the sufficient and early as possible detection of known genetically hearing disorders via umbilical cord analysis. In case of a known familial genetic hearing disorder, it is advisable to analyze newborn siblings for the corresponding genetic defect as soon as possible, to be able to plan and initiate clinical care for the patient as early as possible. It is also extremely important for the parents to obtain clear information about the auditory status of the newborn.

Long-term outcome of vestibular function and hearing in children with congenital cytomegalovirus infection: a prospective cohort study.

PURPOSE: Congenital cytomegalovirus infection (cCMV) is the most frequent nonhereditary cause for sensorineural hearing loss (SNHL) in children. Data on vestibular function in children with cCMV are, however, scarce, although some evidence for cCMV-associated vestibular dysfunction exists. In this prospective cohort study, we evaluated long-term vestibular function and hearing outcomes in a cohort of children with cCMV. METHODS: Participants were 6-7-year-old children with cCMV from a large population-based screening study. Controls were age and gender matched healthy children, who were CMV-negative at birth. Hearing was examined with pure tone audiometry. Definition of hearing loss was pure-tone average > 20 dB. Vestibular function was assessed using the video head impulse test that provides a measure of semicircular canal function. Definition of vestibular dysfunction was lateral semicircular canal gain < 0.75. RESULTS: Vestibular dysfunction occurred in 7/36 (19.4%) of children with cCMV and in 1/31 (3.2%) of controls (p = 0.060). SNHL was recorded in 4/38 (10.5%) of children with cCMV and in 0/33 of controls (p = 0.118). Hearing loss was unilateral in all cases. In cCMV group, the two children with bilateral vestibular dysfunction also had SNHL, whereas those with unilateral vestibular dysfunction (n = 5) had normal hearing. CONCLUSIONS: In this cohort of children with cCMV identified using newborn screening, vestibular dysfunction was more common than SNHL at 6 years of age. Vestibular dysfunction occurred both in children with and without SNHL. Based on these data, inclusion of vestibular tests in follow-up protocol of cCMV should be considered.

Universal newborn hearing screening with automated auditory brainstem response (AABR) in Hungary: 5-year experience in diagnostics and influence on the early intervention.

PURPOSE: In 2015 a new regulation and guidelines for the universal newborn hearing screening by AABR measurement have been implemented in Hungary. The aim of our study was to analyse (1) the past 5 years of data from our diagnostic centre about the incidence and types of congenital hearing losses, and (2) the first experiences with the National Newborn Hearing Screening Registry, started in 2019, and (3) the influence of the screening on the pediatric cochlear implant program. METHODS: 1269 children referred to our diagnostic centre between 2017 and 2021 were investigated. A third AABR measurement and full audiological evaluation were performed. Furthermore, one-year period data of the screening registry, and the number of implanted children at or under the age of 3 were analysed using the national databases. RESULTS: Altogether 276 newborns (22% of the referred cases after the two-stage screening) had hearing loss, 134 (49%) out of them was conductive origin, almost twice frequent in male as in female. Permanent sensorineural hearing impairment was found in 142 (51%), 58 (40%) of them had bilateral, severe to profound hearing loss, occurring more frequently in male as in female. The national digital registration of the screening data within 12 months concerned 68%. The number of early cochlear implantation in one year increased from 1 to 23 children in the past 15 years. CONCLUSION: A third AABR after the two-stage screening increased the efficiency and filtered the 78% false-positive cases. The audiological diagnostics verified and typed the hearing losses ensuring the early intervention.

Application of Cervical Vestibular-Evoked Myogenic Potentials in Adults with Moderate to Profound Sensorineural Hearing Loss: A Preliminary Study

Abstract Introduction The cochlea and the vestibular receptors are closely related in terms of anatomy and phylogeny. Patients with moderate to profound sensorineural hearing loss (MPSHL) should have their vestibular organ functions tested. Objective To evaluate the incidence of vestibular abnormalities in patients with MPSHL and to study the correlation between the etiology of hearing loss (HL) and a possible damage to the labyrinth. Methods A case-control retrospective study was performed. In the case group, 20 adults with MPSHL of known etiology were included. The control group was composed of 15 adults with normal hearing. The case group was divided into 4 subgroups based on the etiology (bacterial meningitis, virus, vascular disease, congenital). Cervical vestibular-evoked myogenic potentials (cVEMPs) were used to rate the saccular function and lower vestibular nerve. Results The study was performed in 70 ears, and it highlighted the presence of early biphasic P1-N1 complex in 29 (71.5%) out of 40 ears in the study group, and in all of the 30 ears in the control group (p = 0.001). Regarding the presence or absence of cVEMPs among the four subgroups of patients with MPSHL, the data were statistically significant (p < 0.001). The comparison between the latencies and amplitude of P1-N1 in case and control groups from other studies and in the four subgroups of cases in the present study did not detect statistically significant differences. Conclusion The present study demonstrates that patients with MPSHL have a high incidence of damage to the labyrinthine organs, and it increases the current knowledge about the etiopathogenesis of sensorineural HL, which is often of unknown nature.

Complete oculocerebrorenal phenotype of Lowe syndrome in a female patient with half reduction of inositol polyphosphate 5-phosphatase.

The oculocerebrorenal disorder of Lowe syndrome is an X-linked mutation in the gene oculocerebrorenal syndrome of Lowe 1 (OCRL), characterized by the triad of congenital cataracts, severe intellectual impairment, and renal tubular dysfunction. Manifestations of phenotype in female carriers and patients are extremely rare. We present a female case with congenital cataracts, severe intellectual impairment, sensorineural hearing loss, and renal tubular dysfunction as Lowe syndrome. A 9-year-old Japanese girl visited our hospital due to prolonged proteinuria. Her renal biopsy revealed diffuse mesangium proliferation, sclerosis and dilatation of renal tubules, and mild IgA deposition in the mesangial region. Furthermore, she had congenital cataracts, severe intellectual impairment, and sensorineural hearing loss. Genetic screening did not identify mutations of the ORCL gene encoding inositol polyphosphate 5-phosphatase (IPP-5P) (46 XX, female). However, we found the reduction of enzyme activity of IPP-5P to 50% of the normal value. Furthermore, her renal function had deteriorated to renal failure within a decade. Finally, she received peritoneal dialysis and renal transplantation. We present the oculocerebrorenal phenotype of Lowe syndrome in a female patient with reduced activity of IPP-5P without OCRL gene mutation.

Is CT necessary for imaging paediatric congenital sensorineural hearing loss?

Objectives: To determine if MRI alone is adequate for pre-operative assessment of paediatric congenital sensorineural hearing loss (SNHL). While aberrant intratemporal facial nerve anatomy is usually occult on MRI, we postulate that the majority of cases have no adverse bearing on surgical outcomes.Methods: MRI and CT of the temporal bones were analysed in 240 children who underwent both on the same day for SNHL. Only children under the age of 5 years with no reported clinical syndrome or dysmorphic external ear anatomy were included.Results and discussion: 169 patients satisfied the inclusion criteria. MRI detected 32/54 cases of cochleovestibular dysplasia, with the majority of the additional CT findings comprising subtle incomplete partition type 2 (IP2) anomalies. Of the 22 cases not evident on MRI, 13 patients also had large vestibular aqueduct syndromoe (LVAS), which would have prompted evaluation with CT due to the near universal co-existence of these entities. Only one patient exhibited aberrant intratemporal facial nerve anatomy that may have conferred surgical risk and was occult on MRI.Conclusion: In a defined paediatric SNHL cohort, the addition of routine temporal bone CT to MRI offers limited additional yield but confers a significant radiation burden on a young population.

Cochlear Implantation Outcomes in Children with Agenesis of the Corpus Callosum: A Retrospective Study and A Review of the Literature.

OBJECTIVES: The aim of the present study was to analyze the outcomes of cochlear implantation (CI) in patients with agenesis of the corpus callosum (CCA). A literature review and a retrospective analysis of our cochlear implant database were performed. MATERIALS AND METHODS: To the best of our knowledge, in the English literature, there was only one case reported with CCA who had undergone CI surgery. This case had Donnai-Barrow syndrome. In the Cukurova University School of Medicine Department of Otorhinolaryngology database, 5 of the 1317 patients who underwent CI surgery who had CCA were selected. The patients' demographic characteristics, operative findings, surgical outcomes, and additional disabilities were investigated. The patients' preoperative and postoperative Listening Progress Profile (LiP) and Meaningful Auditory Integration Scale (MAIS) tests were done to analyze the auditory performances. RESULTS: The participants of the study were 5 (0.38%) individuals (2 male and 3 female patients; ages 5.5, 7.5, 8, 9, and 12 years). Two of the patients had total agenesis, and the other three had partial agenesis of the CCA. In the histories of the patients, one patient had parental consanguinity, and one had febrile convulsion. No patient had an additional disability. None had experienced device failure. No patients were non-users or limited users of cochlear implants. Postoperative LiP and MAIS test scores were improved for all patients nearly as the patients without any deformity. They showed normal auditory performance in the analysis in their postoperative 48 months of follow-up. CONCLUSION: Patients who had CCA are good candidates for CI surgery.

The Long-Term Efficacy of Cochlear Implantation for Hearing Loss in Muckel-Wells Syndrome.

Muckle-Wells syndrome (MWS), a subclass of cryopyrin-associated periodic syndrome (CAPS), sometimes includes complications of bilateral progressive sensorineural hearing loss. A 48-year-old woman had been diagnosed with pediatric rheumatic arthritis at aged 6 years; however, systematic therapy with prednisolone and methotrexate showed limited efficacy for her general fatigue and arthritic pain, and it never improved the hearing level. She underwent a cochlear implant surgery for progressive profound bilateral hearing loss. After 7 years of cochlear implant surgery, she was diagnosed with MWS by genetic tests. Interleukin (IL)-1ß monoclonal antibody therapy (canakinumab) improved general fatigue and arthritic pain but showed no effect on cochlear symptoms. Owing to successful cochlear implant surgery, she reacquired the hearing and communication function while being able to understand over 90% of monosyllables and words in the sound field of her daily life at 65 dB SPL for the next 13 years of her life. This suggests that peripheral cochlear damage induced by chronic inflammation contributes to the sensorineural hearing loss in cases with MWS, and that cochlear implantation can provide long-term hearing efficacy for patients with MWS with irreversible profound hearing loss.

Sensorineural Hearing Loss in Newborns Hospitalized in Neonatal Intensive Care Unit: An Observational Study.

Children hospitalized in Neonatal Intensive Care Units (NICU) present an increased risk for Sensorineural Hearing Loss (SNHL) due to prematurity, hypoxia-ischemia, hyperventilation, low birth weight and the use of ototoxic drugs. The aim of this study was to assess the prevalence of SNHL in newborns hospitalized in a NICU using Transient Evoked Otoacoustic Emissions (TEOAE) and Automated Auditory Brainstem Responses (A-ABR) and analyze the associated risk factors. A sample of 153 newborns hospitalized in NICU underwent TEOAE, A-ABR and clinical ABR to evaluate the presence of hearing deficits. Prevalence of SNHL was calculated and odds ratio for specific risk factors was measured. One-hundred fifteen babies (86.7%) presented normal hearing at TEOAE and A-ABR. Fifteen children had a REFER response at TEOAE and a PASS response at A-ABR. Twenty-five children (16.3%) had a REFER A-ABR and were addressed to clinical ABR. A diagnosis of SNHL was made in 12 (7.8%) newborns. An increased risk of SNHL was observed in preterm children <28 weeks (p=0.0135), in children with neurological disorders (p=0.02), that underwent surgery (p=0.0002), affected from premature retinopathy (p=0.0006), craniofacial malformation (p=0.007) and that had sepsis (p=0.04). Additional risk factors for SNHL in our sample were a maternal disease during pregnancy (p=0.0011), cesarean delivery (p<0.0001) and a twin pregnancy (p<0.0001). SNHL in newborns is correlated with hospitalization in NICU. An accurate hearing screening associated to a rigorous clinical medical collection of data is necessary to promptly identify cases of SNHL in children with a special attention to those hospitalized in NICU and plan proper intervention.

Cochlear implantation in incomplete partition type I.

OBJECTIVES: To share our experience in cochlear implanted patients with incomplete partition type I, to compare it with the literature results and to disclose difficulties facing cochlear implant teams dealing with these patients. MATERIALS AND METHODS: Clinical records of 1089 cochlear implant procedures in a cochlear implant center were reviewed and data of patients who had incomplete partition type I were enrolled in this study. Their auditory and speech performances were evaluated 3 years after the implantation. RESULTS: Eighteen cases (1.65%) had incomplete partition type I. Cerebrospinal fluid gusher was encountered during opening the cochlea in 15 patients (83.3%). There were no cases of persistent CSF leak or postoperative meningitis. In 61.1% of patients, some additional anomalies were found during the operation. Although in 55.6% of cases no electrically evoked compound action potential was detected even in long-term follow-up, all patients had satisfactory auditory and speech outcome. CONCLUSION: Cochlear implantation is a relatively safe and effective treatment for patients who have incomplete partition type I, even if the procedure may be somehow challenging.

New SMS classification of cochleovestibular malformation and its impact on decision-making.

OBJECTIVE: To propose a new classification of inner-ear anomalies that is more clinically oriented and surgically relevant: the SMS (Sawai Man Singh) classification of cochleovestibular malformations. METHODS: A retrospective multicentric study was conducted of 436 cochlear implantations carried out in 3 Indian tertiary care institutes. Patients with anomalous anatomy were included and classified, as per the new SMS classification, into cochleovestibular malformation types I, II, III and IV, based on cochlear morphology, modiolus and lamina cribrosa. RESULTS: There were 19, 23, 8 and 4 patients with cochleovestibular malformation types I, II, III and IV, respectively. Two-year post-operative Meaningful Auditory Integration Scale scores were statistically analysed. CONCLUSION: This new classification for inner-ear anomalies is a simpler, more practical, outcome-oriented classification that can be used to better plan the surgery. These merits make it a more uniform classification for recording results.

DTI study on rehabilitation of the congenital deafness auditory pathway and speech center by cochlear implantation.

PURPOSE: To explore the correlation between hearing and speech recovery levels after cochlear implantation and examined the preoperative microstructure of auditory pathways and speech centre using DTI. METHODS: (1) Fifty-two SNHL children between 0 and 6 years and 19 age and gender matched normal hearing subjects had received 3.0 T-MRI examination of the brain.FA, axial diffusion coefficient (λ‖), radial diffusion coefficient (λ⊥), and MD values in the lateral lemniscus, inferior colliculus, medial geniculate bodies, auditory radiations, Brodmann areas 41, 42, 22, 44, 45, and 39 were all measured bilaterally. (2) CAP and SIR scores were assessed in fourty-six cochlear implantation children at 6 months post-implant. Correlations among deaf children ages, FA value of bilateral inferior colliculus FA values, BA22, BA44, and postoperative CAP, and SIR scores were analyzed using multiple linear regression. RESULTS: The preoperative standard partial regression age coefficient of deaf children (|bi'| = 0.404) was slightly greater than that of the inferior colliculus (|bi'| = 0.377) FA value. CONCLUSION: Preoperative children ages and inferior colliculus FA values were important factors influencing postoperative CAP score. Inferior colliculus FA value is a vital influencing factor in rehabilitation after cochlear implantation.

Frequency of GJB2 mutations in patients with nonsyndromic hearing loss from an ethnically characterized Brazilian population / Frequência de mutações de GJB2 em pacientes com perda auditiva não sindrômica em uma população brasileira etnicamente caracterizada

Abstract Introduction: In different parts of the world, mutations in the GJB2 gene are associated with nonsyndromic hearing loss, and the homozygous 35delG mutation (p.Gly12Valfs*2) is a major cause of hereditary hearing loss. However, the 35delG mutation is not equally prevalent across ethnicities, making it important to study other mutations, especially in multiethnic countries such as Brazil. Objective: This study aimed to identify different mutations in the GJB2 gene in patients with severe to profound nonsyndromic sensorineural hearing loss of putative genetic origin, and who were negative or heterozygote for the 35delG mutation. Methods: Observational study that analyzed 100 ethnically characterized Brazilian patients with nonsyndromic severe to profound sensorineural hearing loss, who were negative or heterozygote for the 35delG mutation. GJB2 mutations were detected by DNA-based sequencing in this population. Participants' ethnicities were identified as Latin European, Non-Latin European, Jewish, Native, Turkish, Afro-American, Asian and Others. Results: Sixteen participants were heterozygote for the 35delG mutation; 14 participants, including three 35delG heterozygote's, had nine different alterations in the GJB2 gene. One variant, p.Ser199Glnfs*9, detected in two participants, was previously unreported. Three variants were pathogenic (p.Trp172*, p.Val167Met, and p.Arg75Trp), two were non-pathogenic (p.Val27Ile and p.Ile196Thr), and three variants were indeterminate (p.Met34Thr, p.Arg127Leu, and p.Lys168Arg). Three cases of compound heterozygosity were detected: p.[(Gly12Valfs*2)];[(Trp172*)], p.[(Gly12Valfs*2)](;)[(Met34Thr)], and p.[(Gly12Valfs*2)(;)[(Ser199Glnfs*9)]). Conclusion: This study detected previously unclassified variants and one case of previously unreported compound heterozygosity.

Resumo Introdução: Em diferentes partes do mundo, mutações do gene GJB2 estão associadas a perda auditiva não sindrômica e a mutação homozigótica 35delG (p.Gly12Valfs*2) é uma das principais causas de perda auditiva hereditária. No entanto, a mutação 35delG não é igualmente prevalente em todas as etnias, faz com que seja importante estudar outras mutações, especialmente em países multiétnicos, como o Brasil. Objetivo: Identificar diferentes mutações no gene GJB2 em pacientes com perda auditiva neurossensorial grave ou profunda não sindrômica de origem genética putativa e negativos ou heterozigotos para a mutação 35delG. Método: Estudo observacional que analisou 100 pacientes brasileiros caracterizados etnicamente, com perda auditiva neurossensorial grave ou profunda não sindrômica, negativos ou heterozigotos para a mutação 35delG. As mutações de GJB2 foram detectadas por sequenciamento baseado no DNA nessa população. As etnias dos participantes foram identificadas como latino-europeia, não latino-europeia, judaica, nativa, turca, negra, asiática e outras. Resultados: Dezesseis participantes eram heterozigotos para a mutação 35delG e 14, incluindo três heterozigotos para 35delG, apresentaram nove alterações no gene GJB2. Uma variante, p.Ser199Glnfs*9, detectada em dois participantes, não havia sido relatada anteriormente. Três variantes eram patogênicas (p.Trp172*, p.Val167Met, e p.Arg75Trp), duas não patogênicas (p.Val27Ile e p.Ile196Thr) e três indeterminadas (p.Met34Thr, p.Arg127Leu, e p.Lys168Arg). Três casos de heterozigosidade composta foram detectados: p.[(Gly12Valfs*2)];[(Trp172*)], p.[(Gly12Valfs*2)](;)[(Met34Thr)], e p.[(Gly12Valfs*2)(;)[(Ser199Glnfs*9)]). Conclusão: Este estudo detectou variantes não classificadas anteriormente e um caso de heterozigosidade composta ainda não relatada.

Epidemiologic, Imaging, Audiologic, Clinical, Surgical, and Prognostic Issues in Common Cavity Deformity: A Narrative Review.

IMPORTANCE: Common cavity deformity is a rare congenital inner ear malformation associated with profound hearing loss and attributed to an early developmental arrest of the cochlear-vestibular structures. This narrative review highlights the need to identify reliable indicators of hearing rehabilitation outcome. OBSERVATIONS: Despite its relatively simple definition, common cavity deformity varies widely in morphologic features, presence of cochlear nerve fibers and remnants of Corti organ, and outcome after cochlear or brainstem implant. CONCLUSIONS AND RELEVANCE: Cochlear implant has been shown to be a valid option for common cavity deformity, but its outcome remains variable and poor. Identification of specific neuroradiologic, audiologic, and neurophysiologic prognostic features; tailoring of the surgical approach; and standardization of outcome measures are needed to optimize the management of common cavity deformity and hearing rehabilitation after implant.