Large Vestibular Aqueduct Syndrome Research Articles

A Three-Year Follow-Up of a Patient With Large Vestibular Aqueduct Syndrome Who Underwent Bilateral Endolymphatic Duct Blockage Surgery

A Three-Year Follow-Up of a Patient With Large Vestibular Aqueduct Syndrome Who Underwent Bilateral Endolymphatic Duct Blockage Surgery

Correlation of Endolysmphatic Duct Signal Intensity With Clinical Features in Otological Diseases.

Bilateral high signal intensity (SI) in the endolymphatic duct (ED) on magnetic resonance imaging (MRI) has been reported as a common characteristic in ears with large vestibular aqueduct syndrome (LVAS). However, the significance of bilateral high SI in the ED remains unknown. The present study aimed to compare the correlation between SI in the ED and the clinical manifestations in various otological disorders and consider the significance of the MRI findings. Retrospective study. University hospital. The study included 2,450 ears from 1,225 patients with various otological disorders. All ears underwent 3T enhanced MRI and were evaluated for the degree of endolymphatic hydrops (EH) and the SI ratios (SIRs; i.e., the calculation between SIs in the ED and those in the cerebellum). The imaging findings were compared with their clinical symptoms. Ears with bilateral high SIRs in the ED tended to have considerably less occurrence of EH in both the cochlea and vestibule than those with bilateral low SIRs. Ears with SIR ≥8 showed significantly elevated hearing thresholds at lower frequencies on pure-tone audiometry, although they exhibited a markedly lower incidence of cochlear EH than those with SIR <8. Moreover, ears with vertigo exhibited notably higher SIRs than those without vertigo. Bilateral high SI in the ED on MRI may reflect pathophysiology underlying sensorineural hearing loss and vestibular symptoms, which are not associated with EH formation.

Advances in vestibular function and rehabilitation of large vestibular aqueduct syndrome

Large vestibular aqueduct syndrome（LVAS） is a common recessive hereditary hearing loss disease, and some patients may also experience vestibular dysfunction. With the wide application of cochlear implant（CI） and the development of vestibular medicine, the pathophysiological mechanism of LVAS and the influence mechanism of CI on vestibular function are gradually elucidated. Consequently, the evaluation and rehabilitation of vestibular dysfunction function have also become research hotspots. This article reviews studies on vestibular function and related rehabilitation in patients with large vestibular aqueduct syndrome.

Predictive accuracy of wideband absorbance in children with large vestibular aqueduct syndrome: A single-center retrospective study

ObjectivesThis study aimed to assess the clinical significance of Wideband Absorbance (WBA) in children with Large Vestibular Aqueduct Syndrome (LVAS), which could potentially serve as diagnostic and predictive markers for LVAS in children. DesignThis was a single-center retrospective case-control study. Audiological measurements and Wideband Acoustic Immittance (WAI) were performed. Propensity score matching (PSM) was considered to treat group imbalance. The Receiver Operating Characteristic (ROC) curves and area under the ROC curve (AUC) were used to evaluate the sensitivity and specificity of WBA. Study sampleParticipants included 42 children with LVAS and 163 normal children aged 6 months −11 years recruited from clinical audiology settings between 2019 and 2021. ResultsThe WBA at Tympanometric Peak Pressure (WBATPP) and Ambient Pressure (WBAA) in the LVAS group were significantly lower than those of the control group at 1259–2000 Hz but higher at 4000–6349 Hz (p < 0.05, power >0.8). The WBAA (1587 Hz) AUC value was 0.805, identifying a score ≤0.565 as indicative of a LVAS risk. ConclusionsWBA holds promise in distinguishing LVAS from the normal condition and warrants further exploration as a tool to examine the influence of inner ear pressure on acoustic energy transmission in the middle ear.

Update on diagnostic procedures in third window syndromes. German version

The diagnosis of third window syndromes often poses achallenge in clinical practice. This paper provides an up-to-date overview of diagnostic procedures in third window syndromes, with special emphasis on superior canal dehiscence syndrome(SCDS), large vestibular aqueduct syndrome(LVAS), andX-chromosomal malformation of the cochlea. Aliterature search was performed in PubMed up to December 2023. Furthermore, aselection of the authors' own cases is presented. Audiovestibular tests for the diagnosis of third window syndromes are most often reported for patients with SCDS in the literature. In this context, cut-off values with different sensitivities and specificities have been defined for different outcome parameters of vestibular evoked myogenic potentials. Current developments include the application of electrocochleography, broadband tympanometry, video head impulse testing, and vibration-induced nystagmus. Genetic analyses are increasingly applied in LVAS. The diagnosis of third window syndromes is always based on the synthesis of patients' symptoms, clinical signs, audiovestibular test results, and imaging.

Wideband acoustic immittance characteristics and machine learning-based diagnostic model for children with large vestibular aqueduct syndrome

Objective:This study was to investigate the wideband acoustic immittance（WAI） characteristics of children with large vestibular aqueduct syndrome（LVAS） and to construct a diagnostic model for LVAS based on WAI and machine learning（ML） techniques. Methods:We performed a retrospective analysis of the data from 38 children（76 ears） with LVAS and 44 children（88 ears） with normal hearing. The data included conventional audiological examination, temporal bone CT scan and WAI test. We performed statistical analysis and developed multivariate diagnostic models based on different ML techniques. Results:The two groups were balanced in terms of ear, gender, and age（P>0.05）. The wideband absorbance（WBA） of the LVAS group was significantly lower than that of the control group at 1 000-2 519 Hz, while the WBA of the LVAS group was significantly higher than that of the control group at 4 000-6 349 Hz（P<0.05）. WBA at 5 039 Hz under ambient pressure had a certain diagnostic value（AUC=0.767）. The multivariate diagnostic model had a high diagnostic value（AUC>0.8）, among which the KNN model performed the best（AUC=0.961）. Conclusion:The WAI characteristics of children with LVAS are significantly different from those of normal children. The diagnostic model based on WAI and ML techniques has high accuracy and reliability, and provides new ideas and methods for intelligent diagnosis of LVAS.

A Long-Term Follow-Up Study on the Auditory Performance and Speech Intelligibility of Mandarin-Speaking Prelingually Deaf Children With Isolated Large Vestibular Aqueduct Syndrome After Cochlear Implantation.

The purpose of this study was to evaluate the auditory performance and speech perception of 104 children with isolated large vestibular aqueduct syndrome (LVAS) and 523 children with no inner ear malformation (IEM) for 5 years after cochlear implantation, in order to explore whether isolated LVAS can affect the long-term hearing and speech rehabilitation of deaf children after cochlear implantation. A cohort study was established consisting of 627 children who underwent cochlear implantation at Beijing Tongren Hospital from 1999 to 2016. The children were examined at 0, 6, 12, 24, 36, 48, and 60 months after cochlear implantation to assess their auditory performance and speech perception using the Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) questionnaires. The CAP scores of the isolated LVAS group increased significantly during the baseline to the 24th month, after which they gradually rose until reaching the plateau during the 24th to the 60th month. The CAP scores of the non-IEM group increased significantly during the baseline to the 36th month and then increased steadily. The SIR scores went up significantly during the baseline to the 48th month, and increased in a gradual manner in other stages of isolated LVAS evaluation. In comparison, The SIR scores of non-IEM group grew remarkably from the baseline to the 60th month. There were no significant differences in the CAP or SIR scores between isolated LVAS and non-IEM groups in each stage of evaluation, with the only exception being the CAP score at baseline month after cochlear implantation. The CAP and SIR questionnaires are helpful tools for quantifying the early hearing and speech skills of younger prelingually deafened cochlear implant recipients. This long-term follow-up study shows that the speech and hearing development of children in isolated LVAS and non-IEM groups follow similar patterns, and isolated LVAS does not affect the long-term rehabilitation of deaf children after cochlear implantation.

Characteristics of vestibular-evoked myogenic potentials in children with vestibular malformation and severe sensorineural hearing loss

BackgroundWith the increasing clinical focus on the safety of bilateral cochlear implantation (CI) and the potential risk of bilateral vestibular dysfunction, evaluating vestibular end-organ function in patients with vestibular malformations with accompanying abnormalities has been strongly recommended. ObjectivesTo identify the vestibular-evoked myogenic potential (VEMP) values among children with sensorineural hearing loss (SNHL) with vestibular malformation and assess the effectiveness of VEMP testing for inner ear malformations (IEM) diagnosis. MethodsThis study included 96 children (192 ears), including those with vestibular malformations (48 ears), large vestibular aqueduct syndrome (LVAS) (50 ears), and SNHL without IEM (94 ears; control group). All groups underwent ocular and cervical VEMP (oVEMP and cVEMP, respectively) testing. The response rates, VEMP parameters, and wave characteristics were compared. ResultsThe cVEMP response rates were 37.5 %, 64 %, and 58.51 % and the oVEMP response rates were 42.86 %, 78.95 %, and 77.27 % in the vestibular malformation, LVAS, and control groups, respectively, and significantly differed between groups (cVEMP: X2 = 18.228, P<0.001) (oVEMP: X2 = 7.528, P = 0.023). Significant inter-group differences were observed for the cVEMP and oVEMP latency and amplitude (P < 0.05). The LVAS group's waveform exhibited a prolonged latency and increased amplitude compared with that of the other groups. ConclusionPatients with SNHL were highly susceptible to otolith dysfunction, regardless of comorbid vestibular malformation presence. Measuring VEMPs is an effective and rapid evaluation technique for vestibular function and could provide a basis for vestibular rehabilitation training.

Analysis of 59 cases of large vestibular aqueduct syndrome SLC26A4gene mutation frequency and new mutation sites

Objective:To study the frequency of SLC26A4 gene mutation sites in children with enlarged vestibular aqueduct deafness in Yunnan, report the new mutation sites of SLC26A4 gene, further clarify the mutation spectrum of SLC26A4gene, and explore the association between biallelic and monoallelic mutations of SLC26A4 gene and CT phenotype of inner ear, so as to provide basis for clinical and genetic diagnosis of deafness. Methods:Review the results of temporal bone CT examination of 390 children after cochlear implantation in the Department of Otolaryngology, Kunming Children's Hospital from August 2016 to September 2021. Sanger sequencing of SLC26A4 gene was performed in 59 children with enlarged vestibular aqueduct. According to the genetic test results, the children who underwent temporal bone CT examination were divided into two groups: SLC26A4 biallelic mutation group（homozygous mutation and compound heterozygous mutation）, monoallelic mutation group, and the association with inner ear CT phenotype was analyzed, and the new sites were summarized and analyzed. Results:The c.919-2a>g mutation was the most common mutation in children with enlarged vestibular aqueduct with SLC26A4 gene mutation. Three new variants of SLC26A4 gene were found; CT examination combined with genetic testing found that a part of children with enlarged vestibular aqueduct was associated with SLC26A4 monoallelic mutation or no SLC26A4 gene mutation was detected. Further research is needed to investigate the involvement of other pathogenic factors in the pathogenesis of EVA.

Follow-up of infants with mild-to-moderate sensorineural hearing loss over three years.

To observe and analyse the hearing outcome in infants with mild-to-moderate sensorineural hearing loss (SNHL) who failed universal newborn hearing screening (UNHS). This retrospective cohort analysis included infants with mild-to-moderate SNHL and with complete etiological diagnosis and followed up over three years. Out of 96 infants with mild-to-moderate SNHL 72 were stable (75%). Only one case was normal (1.04%), ten cases were improved (10.42%), and 13 were deteriorated (13.54%). The pathogenic mutation of GJB2 was the most common cause (50/96, 52.08%), and most of them were homozygous or complex heterozygous mutations of p.V37I (44/50, 88%). There were 11 cases (11.49%) with large vestibular aqueduct syndrome (LVAS) and nine cases (9.38%) with perinatal risk factors. Infants with GJB2 pathogenic mutation and those without certain etiology mostly had unchanged hearing levels, accounting for 84% (42/50) and 84.61% (22/26), respectively. Hearing deterioration in LVAS was associated with seven cases (63.64%). There was no difference in types of outcomes in perinatal risk factor infants, who were more likely to improve than the other groups, but there were three cases (33.3%) deteriorated to profound hearing loss. Comparison of outcomes of different etiologies showed statistically significant difference (Chi-square=28.673, p=0.000). Normal and improved hearing in infants with mild-to-moderate SNHL was rare before the age of three, unlike in many previous studies, and appropriate intervention is recommended. However, intervention should be adjusted according to the hearing outcomes because of the possibility of improvement or deterioration. The etiological diagnosis of infants with mild-to-moderate SNHL would be helpful for predicting the outcome and managing intervention.

Characteristics of large vestibular aqueduct syndrome in wideband acoustic immittance.

To describe the characteristics of large vestibular aqueduct syndrome (LVAS) in wideband acoustic immittance (WAI) and to explore whether inner ear deformity has an impact on WAI results. Subjects with typical LVAS (LVAS group) and control subjects with a normal anatomical structure of the inner ear (control group) were screened from pediatric patients with cochlear implants using thin-slice computed tomography (CT) images of the temporal bone. With inflammation of the auditory canal and middle ear excluded by routine ear examination and 226 Hz acoustic immittance, WAI data were acquired. Then, the maximum absorbance as the major observation indicator on the mean tympanogram was compared between the LVAS group and control group, and a descriptive comparison of the mean tympanogram and frequency-absorbance curve at peak pressure was performed between the two groups. The LVAS group included 21 cases (38 ears), and the control group included 27 cases (45 ears). All LVAS subjects met the Valvassori criteria, and the VA at the horizontal semicircular canal displayed flared expansion. On the mean tympanogram, the maximum absorbance in the LVAS group (0.542 ± 0.087) was significantly higher than that in the control group (0.455 ± 0.087) (p < 0.001). The tympanogram in the LVAS group showed an overall elevation, and the absorbance at all pressure sampling points was significantly higher than that in the control group (p < 0.001). The frequency-absorbance curve at peak pressure first increased and then decreased in both groups, and the LVAS group showed higher absorbance than the control group in the frequency range below 2,828 Hz. The absorbance at 343-1,124 Hz was significantly different between the two groups (p < 0.001), and 343-1,124 Hz was the major frequency range at which the maximum absorbance on the mean tympanogram increased in the LVAS group. Large vestibular aqueduct syndrome (LVAS) shows increased absorbance in low and medium frequency ranges in WAI. The maximum absorbance on the mean tympanogram can serve as a reliable evaluation indicator. Inner ear factors must be considered when middle ear lesions are analyzed by WAI.

Fluid-solid coupling model and biological features of large vestibular aqueduct syndrome.

Objective: Computed tomography (CT) images of the temporal bone of large vestibular aqueduct syndrome (LVAS) patients were used to establish 3D numerical models based on the structure of the inner ear, which are, in turn, used to construct inner ear fluid-solid coupling models. The physiological features and pathophysiology of LVAS were analyzed from a biomechanical perspective using finite element analysis. Methods: CT images of the temporal bone were collected from five children attending the Second Hospital of Dalian Medical University in 2022. The CT images were used to build 3D models of the inner ear containing the vestibular aqueduct (VA) by Mimics and Geomagic software, and round window membrane models and fluid-solid coupling models were built by ANSYS software to perform fluid-solid coupling analysis. Results: By applying different pressure loads, the deformation of the round window membranes occurred, and their trend was basically the same as that of the load. The deformation and stress of the round window membranes increased with the increase in load. Under the same load, the deformation and stress of the round window membranes increased with the expansion of the midpoint width of the VA. Conclusion: CT images of the temporal bone used clinically could establish a complete 3D numerical model of the inner ear containing VA. Fluctuations in cerebrospinal fluid pressure could affect inner ear pressure, and VA had a limiting effect on the pressure from cerebrospinal fluid. The larger the VA, the smaller the limiting effect on the pressure.

Hearing Loss Related to Gene Mutations in Distal Renal Tubular Acidosis

Introduction: Distal renal tubular acidosis (dRTA) is a disease that may develop either primarily or secondarily, resulting from urinary acidification defects in distal tubules. Hearing loss may accompany primary forms of dRTA. This study aims to determine the characteristics of hearing loss due to different gene mutations in patients with dRTA. Methods: Behavioral and electrophysiological audiological evaluations were performed after otolaryngology examination in 21 patients with clinically diagnosed dRTA. Radiological imaging of the inner ear (n = 9) was conducted and results of genetic analyses using next-generation sequencing method (n = 16) were included. Results: Twenty-one patients with dRTA from 20 unrelated families, aged between 8 months and 33 years (median = 12, interquartile range = 20), participated. All patients with ATP6V1B1 mutations (n = 9) had different degrees of hearing loss. There was one patient with hearing loss in patients with ATP6V0A4 mutations (n = 6). One patient with the WDR72 mutation had normal hearing. Large vestibular aqueduct syndrome (LVAS) was detected in 6 (67%) of 9 patients whose radiological evaluation results were available. Conclusions: LVAS is common in patients with dRTA and may influence the type and severity of hearing loss in these patients. The possibility of both congenital and late-onset and progressive hearing loss should be considered in dRTA patients. A regular audiological follow-up is essential for the early detection of a possible late-onset or progressive hearing loss in these patients.

Advances in the study of fluctuating sensorineural hearing loss

Fluctuating sensorineural hearing loss（FSNHL） is a special type of sensorineural hearing loss, which can be manifested in many clinical diseases. In this paper, some clinical diseases associated with FSNHL are summarized, such as Meniere's disease, large vestibular aqueduct syndrome, acute low frequency sensorineural hearing loss, delayed endolymphatic hydrops, autoimmune inner ear disease and syndromes leading to FSNHL. The pathogenesis, diagnosis and treatment of FSNHL were summarized in order to improve clinicians' understanding of FSNHL, reduce the probability of misdiagnosis of related diseases and improve the prognosis of patients.

Single-cell whole-genome sequencing, haplotype analysis in prenatal diagnosis of monogenic diseases.

Monogenic inherited diseases are common causes of congenital disabilities, leading to severe economic and mental burdens on affected families. In our previous study, we demonstrated the validity of cell-based noninvasive prenatal testing (cbNIPT) in prenatal diagnosis by single-cell targeted sequencing. The present research further explored the feasibility of single-cell whole-genome sequencing (WGS) and haplotype analysis of various monogenic diseases with cbNIPT. Four families were recruited: one with inherited deafness, one with hemophilia, one with large vestibular aqueduct syndrome (LVAS), and one with no disease. Circulating trophoblast cells (cTBs) were obtained from maternal blood and analyzed by single-cell 15X WGS. Haplotype analysis showed that CFC178 (deafness family), CFC616 (hemophilia family), and CFC111 (LVAS family) inherited haplotypes from paternal and/or maternal pathogenic loci. Amniotic fluid or fetal villi samples from the deafness and hemophilia families confirmed these results. WGS performed better than targeted sequencing in genome coverage, allele dropout (ADO), and false-positive (FP) ratios. Our findings suggest that cbNIPT by WGS and haplotype analysis have great potential for use in prenatally diagnosing various monogenic diseases.

Vestibular Loss in Children Affected by LVAS and IP2 Malformation and Operated with Cochlear Implant.

This is a single center cohort study regarding the prevalence of vestibular loss in hearing impaired children affected by large vestibular aqueduct syndrome (LVAS) with incomplete cochlear partition malformation type II (IP2), fitted with cochlear implant (CI). Twenty-seven children received CI operations at 0.4-13 years on one or both ears and tested for vestibular loss with head impulse test, video head impulse test, mini ice-water test and cervical VEMP. Vestibular loss was found in 19% of operated ears and in 13.9% of non-operated ears. The difference was not statistically significant and was not significantly modified by age at implantation, age at testing, sex, presence of SLC26A4 gene mutation or bilaterality. However, the presence of anatomic anomalies at the level of the vestibulum or semicircular canals was significantly associated with a higher incidence of vestibular loss in CI operated children but not in those non-operated. No other factors, such as the surgical access, the electrode type, the presence of Gusher perioperatively, or post-operative vertigo modified significantly the prevalence of vestibular loss. In conclusion, LVAS/IP2 appears to be the major determinant of vestibular loss in these children, with a less obvious impact of CI, excluding the cases with vestibulum/canal anomalies: this group might have a higher risk for vestibular loss after CI surgery.

Retracted: Prediction of Hearing Prognosis of Large Vestibular Aqueduct Syndrome Based on the PyTorch Deep Learning Model.

[This retracts the article DOI: 10.1155/2022/4814577.].

Three-dimensional wideband absorbance immittance findings in young adults with large vestibular aqueduct syndrome.

To investigate the effect of large vestibular aqueduct syndrome (LVAS) on middle ear sound transmission using wideband absorbance immittance (WAI). WAI results from young adult LVAS patients and normal adults were compared. Averaged energy absorbance (EA) at ambient and peak pressure in the LVAS group showed differences to the normal group. Under ambient pressure, the average EA of the LVAS group was significantly higher than the normal group at frequencies 472-866 Hz and 6169-8000 Hz (p< .05) and lower at frequencies 1122-2520 Hz (p< .05). Under peak pressure, absorbance was increased at frequencies 515-728, 841, and 6169-8000 Hz (p< .05) and decreased at 1122-1374Hz and 1587-2448 Hz (p< .05). An investigation into the effect of external auditory canal pressure on EA across frequencies in the pressure-frequency domain, showed that EA differed significantly in the low-frequency region of 707and 1000 Hz from 0 to 200 daPa and 500 Hz at 50 daPa (p< .05). There was also a significant difference in EA between the two groups at 8000 Hz (p< .05) in the pressure range -200-300 daPa. WAI is a valuable tool to measure the effect of LVAS on middle ear sound transmission. LVAS has a significant effect on EA at low and mid frequencies under ambient pressure, while the frequencies affected are mainly at low frequencies when positive pressure is presented. Level 3a.

Research progress in accurate diagnosis of large vestibular aqueduct syndrome

大前庭导水管综合征（LVAS）是常见的隐性遗传性听力损失疾病。LVAS患者可表现为双耳对称或非对称性的、波动或进行性听力损失，部分为迟发性听力损失；具有低频气骨导差，高频感音神经性听力损失、出现声诱发短潜伏期负反应等临床特点；颞骨高分辨CT（HRCT）和内耳核磁共振（MRI）相结合的影像学检查是诊断的金标准；深入分析SLC26A4基因型，加强SLC26A4单等位基因突变者的遗传学研究，并重视EPHA2、FOXI1和KCNJ10基因等与SLC26A4的协同致病性。大前庭导水管综合征的影像学诊断、听力学诊断和基因诊断三个方面彼此补充且相互结合，可进一步实现其精准诊断。.

Advances in vestibular testing in patients with large vestibular aqueduct syndrome

大前庭水管综合征（large vestibular aqueduct syndrome，LVAS）是临床常见的遗传性听力障碍疾病。近年来，有关该病前庭障碍的报道逐渐增多，目前已知该病的前庭症状具有多样性。新型前庭功能检查技术，如前庭诱发肌源性电位、视频头脉冲试验的开展，使得临床上可以深入了解LVAS的前庭病理生理机制。如LVAS患者前庭诱发肌源性电位具有低阈值、高幅值的特点，这符合“内耳第三窗”疾病的特点；而且，其冷热试验/视频头脉冲试验结果的分离性与“内淋巴积水”疾病相一致。随着LVAS人工耳蜗植入手术的开展，与之相关的前庭症状及前庭功能改变也见诸报道。因此，回顾LVAS相关的前庭评估（症状与前庭功能检查），有助于探寻其病理生理机制，有助于在进行临床决策时，除听力外兼顾患者的前庭功能，从而提高患者生活质量。.