Review the EVA-Focused Research Library

The purpose of this work is to identify the role of incomplete partition type II on hearing loss among patients with enlarged vestibular aqueduct (EVA).

https://pubmed.ncbi.nlm.nih.gov/28793961/

This study is a meta-analysis of patient-level data that describes EVA, progressive SNHL, and head trauma, using articles identified on systematic review. 23 studies analyzing 1115 ears with EVA met inclusion criteria. Progressive SNHL was found in 39.6% of ears, with trauma-associated progression in 12%. One important conclusion from this study is that long-term progression of SNHL in patients with EVA is common, but its association with head trauma is not strongly supported.

The aim of this study was to evaluate the use of volumetric HRCT measurements in the diagnosis of enlarged vestibular aqueduct syndrome (EVAS) and describe the association of this novel radiographic approach with clinical hearing outcomes. We hypothesized that volumetric measurements may have stronger correlation to hearing loss given the anatomic variability of the vestibular aqueduct in linear measurements.

https://pubmed.ncbi.nlm.nih.gov/35183013/

To investigate any meaningful differences in hearing between patients with unilateral and bilateral enlarged vestibular aqueduct (EVA). EVA is a common radiological finding in children presenting with hearing loss. We hope to provide insight into the pathogenesis of EVA and provide further guidelines for unilateral EVA management. We hypothesized that hearing loss in unilateral EVA would be similar to that seen in bilateral EVA.

https://pubmed.ncbi.nlm.nih.gov/30634102/

We are quite happy to say that this is our very own work. We looked at electronic medical records from the past fifteen years, and looked for a relationship between vestibular aqueduct midpoint width and hearing loss. This work was unique in the sense that we looked at every single one of each patient's hearing test results, rather than a before/after or single-measurement model of hearing. As a result, we were able to precisely identify a positive relationship between vestibular aqueduct midpoint width and hearing loss, where each extra millimeter of midpoint width is associated with an increase of about 17.5 dB in speech reception threshold and a decrease of 21% in word recognition score.

Computed tomography (CT) has been used in the assessment of pediatric hearing loss, but concern regarding radiation risk and increased utilization of magnetic resonance imaging (MRI) have prompted us toward a more quantitative and sophisticated understanding of CT's potential diagnostic yield. Data from studies describing the use of CT in the diagnostic evaluation of pediatric patients with hearing loss of unknown etiology were evaluated, according to a priori inclusion/exclusion criteria. In 50 criteria-meeting studies, the overall diagnostic yield of CT ranged from 7% to 74%, with the strongest and aggregate data demonstrating a point estimate of 30%. This estimate corresponded to a number needed to image of 4 (range, 2-15). The most common findings were enlarged vestibular aqueduct and cochlear anomalies. The largest studies showed a 4% to 7% yield for narrow cochlear nerve canal. These data, along with similar analyses of radiation risk and risks/benefits of sedated MRI, may be used to help guide the choice of diagnostic imaging.

This study looks at 11 cases of cochlear implantation, reporting 5 bilateral and 6 unilateral cases of EVA out of 827 subjects implanted over a 22 year period. The authors report no postoperative complications, and explain that all the patients regained "serviceable" hearing and returned to normal work/school life.

This article reviews recommended tests for people with hearing loss, in particular, looking to establish clear guidelines about optimal implementation and sequence of genetic tests. Audiometric and etiological data of patients from the otogenetics clinic in the study were collected and analyzed. In 81.2% of the patients, a cause of hearing loss could be determined or suspected. In total, 65.4% had a (presumably) genetic etiology, with connexin 26 (GJB2) mutations as the leading cause. Inquiry of risk factors, associated with congenital hearing loss, and pedigree analysis were found to have the highest diagnostic gain (61.3% and 41.8%). Connexin 26 gene mutations were only present in bilateral hearing impairment, whereas CT abnormalities were related to unilateral (P=0.003), profound (P<0.001) hearing loss. An enlarged vestibular aqueduct was present in 42.9% of all CT abnormalities. Ophthalmologic anomalies were detected in 35.7% of the studied patients. The study concluded that a sequential approach for the etiological diagnosis of unidentified hearing loss could determine or suggest a cause in more than 80% of patients. The approach may vary based on the presenting phenotype.

This article reviews radiographic approaches to evaluating hearing loss, and provides recommendations on which tests to perform first. Children with hearing loss (without suspected cancer, infectious or inflammatory causes), should undergo fast spin-echo T2-weighted MRI or CISS imaging protocols without IV contrast. 5% of patients with unilateral SNHL have bilateral findings on imaging. This can provide prognostic information. This article notes that EVA is the most common imaging finding in patients with SNHL, where findings are bilateral in up to 87% of patients and associated with a cochlear malformation in 84%.

To investigate patient-specific characteristics that independently predict for progressive hearing loss in patients with enlarged vestibular aqueduct (EVA). Utilize multivariable predictive models to identify subgroups of patients with significantly different progression risks.

https://pubmed.ncbi.nlm.nih.gov/34792801/

The genetics of EVA remain elusive, likely as a result of the complexity involved in both genetics generally and EVA specifically. Here, He and coauthors report a new mutation that is associated with EVA, and find that modern genetics models predict this mutation to be damaging. As a result, the authors both identified a new EVA-related mutation and demonstrated that this mutation could be harmful.

This article shows that 22% of patients with EVA as a result of SLC26A4 mutation report balancing issues, despite 45% of patients testing positive for vertigo in one ear. They note that balance is related to hearing ability at low frequencies, but that their tests showed no relationship to genetic or anatomic factors.

The study is a meta-analysis including 29 studies that evaluated 2434 patients with MRIs and 1451 patients with CTs that met inclusion/exclusion criteria. There was a wide range of diagnostic yield from MRI. Heterogeneity among studies was substantial but improved with subgroup analysis. Meta-analysis of yield differences demonstrated that CT had a greater yield than MRI for enlarged vestibular aqueduct (yield difference 16.7% [95% CI, 9.1%-24.4%]) and a borderline advantage for cochlear anomalies (4.7% [95% CI, 0.1%-9.5%]). Studies were more likely to report brain findings with MRI.

The authors of this paper sought to understand what happens when a person has two copies of a mutated gene that is associated with EVA. Because a gene can span a large sequence of DNA, the authors paid close attention to the particular location and type of mutation. They found a potential association between the specific types of mutation and levels of residual hearing, possibly paving the way for further studies into the relationship between types of mutations and hearing loss.

The authors of this study examined three genes in 46 different EVA-affected patients with the goal of developing a genetic test to identify EVA. These three genes are the most commonly-associated with EVA, and are called "SLC26A4", "FOXI1", and "KCNJ10". Their diagnostic test identified mutations in 87% of the subjects, and identified both maternal and paternal mutations in 59% of their population. Working on the assumption that two mutated copies is a stronger indicator of EVA, the authors conclude that their test can identify up to 59% of people with EVA solely using genetic data. This would open the door to EVA diagnosis before hearing loss is discovered, potentially allowing patients and healthcare providers to start thinking about EVA even before birth.

To analyze audiometric outcomes after bilateral cochlear implantation in patients with isolated enlarged vestibular aqueduct (EVA) syndrome and associated incomplete partition (IP) malformations. Secondary objective was to analyze rate of cerebrospinal fluid (CSF) gusher in patients with IP-EVA spectrum deformities and compare this with the existing literature.

https://pubmed.ncbi.nlm.nih.gov/26756161/

For people with profound hearing loss, sometimes the best treatment is cochlear implantation. The authors of this work discuss their experiences performing cochlear implantation in 55 patients who had either Pendred or non-syndromic EVA. They note that 36% of implantations had complications, where 5% were major complications. In 10% of cases, the patients undergoing implantation had “gushing” or “oozing”, which the authors explain was associated with post-operative vertigo. For people with EVA who undergo cochlear implantation, this sort of information could be quite useful to set expectations and help guide decisions regarding cochlear implantation.

This is a large study that examines gene sequences of the SLC26A4 gene in 100 patients with bilateral EVA, selected from a larger group of 1511 patients registered in a Japanese hearing loss gene bank. The authors found that 82% of EVA patients had mutations in SLC26A4, and compared this finding to mutation rates among different ethnic populations. This high mutation rate is consistent with that found by other studies of east Asian populations, for example 97.9% in a Chinese cohort and 92% in a Korean cohort. In contrast, only 20% of Americans with EVA have SLC26A4 mutations. Further, still among patients with EVA, the mutations found in Asian populations are different than those found in Caucasian patients. The authors also conclude that, among the patients in this study, there appeared to be wide variation in hearing levels, even within the same genotypes.

This is one of the largest studies of EVA, providing analysis of 380 patients' data from hospitals all over Japan. They were able to conclude that age greater than ten years, bilateral EVA, a history of head trauma, and Pendred syndrome were all significant risk factors for fluctuating hearing loss and vertigo or dizziness.

The goal of this study was to identify factors associated with sudden drops in hearing level after minor head trauma in patients with an enlarged vestibular aqueduct (EVA). This is a meta-analysis with pooled data of 31 articles included 179 patients with 351 EVAs. Drops in hearing level after minor head trauma were experienced by 34% of the patients. A significant association between sudden deterioration of hearing after minor head trauma and preexisting fluctuating hearing loss (HL) (odds ratio, 8.6; p < 0.001; 95% confidence interval, 3.9-19.3) was found. The diameter of the VA, type of preexisting HL, severity of HL, preexisting progressive HL, and the diagnosis of Pendred syndrome were not significantly associated with sudden drops in hearing levels after head trauma. Only one-third of the patients with a proven EVA experienced sudden drops in hearing level because of head trauma. There is a significant association between preexisting fluctuating HL and the chance of sudden drops in hearing level caused by trauma. Stringent lifestyle advice, like avoiding activities with a risk of minor head trauma such as contact sports, might be restricted to patients with a fluctuating HL and those with a history of sudden drops on minor head trauma.

The anatomy of EVA isn’t the same across all patients, so the goal of this study was to determine if there is any genetic basis for different types of anatomy. A cohort of 47 patients was examined, all of whom were diagnosed with EVA according to the standard CT imaging of the inner ear. Then, the researchers assigned patients into four groups by the location of anatomical difference: (1) aperture wider than the midpoint, (2) aperture and midpoint equally wide, (3) midpoint wider than aperture, and (4) borderline enlargement (less than 1.5mm). 44% of subjects fell into category 1; 11% into category 2; 9% into category 3; and 36% into category 4. 97% of subjects in categories 1, 2, and 3 tested positive for SLC26A4 mutation, compared to 39% of patients in category 4. The specific mutations and levels of hearing loss, however, did not significantly correlate to the patient category.

Recessive mutations of SLC26A4 are a major cause of hearing impairment associated with enlarged vestibular aqueduct (EVA). In a significant percentage of non-syndromic EVA patients, however, only mono-allelic mutations of SLC26A4 can be identified. The aim of this study was to evaluate whether the presence of mono-allelic mutations of SLC26A4 in those patients was coincidental or etiologically associated with the disorder. This was accomplished by sequencing the exons and flanking splicing sites of SLC26A4 in 150 Chinese Han deaf probands with non-syndromic EVA. Two frequent mutations of SLC26A4 in Chinese Hans, were screened by an allele-specific PCR-based array in 3056 ethnically-matched normal hearing controls. The frequency of mono-allelic mutations was determined in each group. Bi-allelic, mono-allelic and no mutation of SLC26A4 were detected in 98 (65.3%), 18 (12%) and 34 (22.67%) deaf probands with non-syndromic EVA, respectively. The frequency of mono-allelic mutations were significantly higher in the 150 deaf probands with non-syndromic EVA (8.67%) than in the 3056 normal hearing controls. The study concluded that the presence of mono-allelic mutations of SLC26A4 in non-syndromic EVA patients is etiologically associated with this disorder. Additional genetic or environmental causes may be present and further investigation would be helpful.

The purpose of this work is to explore audiometry following cochlear implantation (CI) in patients with enlarged vestibular aqueduct (EVA) and to investigate the effects of inner ear morphological variation on post CI audiometry.

https://pubmed.ncbi.nlm.nih.gov/30153950/

The study describes the clinical experience and outcomes of cochlear implantation (CI) in children with isolated enlarged vestibular aqueduct (IEVA) vs. children with enlarged vestibular aqueduct (EVA) associated with other bony labyrinth abnormalities. The clinical course and outcomes of 55 children with EVA undergoing CI between 1991 and 2013 were reviewed. Test measures included speech perception tests, and various speech and language measures. In 18 children (32.7%), IEVA was the only defect present. In 33 children (60%), EVA occurred concomitantly with incomplete partition type 2 (IP 2) bilaterally, and three children with incomplete partition type 1 bilaterally. Ninety-two percent (51 of 55) occurred bilaterally and had matching bony defects. Mean age of CI was 73.4 months. A statistically significant defect-related and linguistic-status pattern was noted. IEVA children demonstrated superior performance on speech perception tests and speech and language tests. The study concluded that children with hearing loss secondary to EVA respond well to cochlear implantation. However, the severity of temporal bone anomalies in these children has clinical relevance.

This article provides an overview of the typical diagnostic workup for a child with SNHL. Typically, patients undergo thorough otolaryngologic and audiometric evaluations, including laboratory tests and temporal bone imaging. These tests may prompt additional consultation with geneticists or ophthalmologists. A sequential diagnostic approach (outlined in the article) has been shown to be both prudent and cost-effective. While a definitive cause is still being established, hearing amplification and a comprehensive treatment plan are noted as the best way to avoid developmental delay and missed milestones. For patients whose EVA is identified on the temporal bone imaging, the authors advocate genetic testing for mutations in the SLC26A4 gene.

The study looks to determine the distribution of the number and types of mutant alleles of SLC26A4 and their correlations with hearing phenotypes in Korean bilateral enlargement of vestibular aqueduct (EVA) patients. The SLC26A4 gene was sequenced for 56 patients with bilateral EVA, and the relationships of these sequences to hearing ability were analyzed based on 0.5-, 1-, 2-, and 3-kHz air conduction averages of pure-tone audiometry. Most patients with bilateral EVA (83.9%) carried two mutant versions of SLC26A4 (“M2”), and all others (16.1%) had only one detectable mutant allele of SLC26A4 (“M1”). There was no significant difference in hearing threshold, progression, or fluctuation of hearing level between the M1 and M2 groups. However, focusing on the type of mutations exclusively in the M2 group, some mutations were associated with more frequent progression of hearing loss during the follow-up period. The study concluded that the auditory phenotype of Korean bilateral EVA patients is more strongly correlated with the type rather than the number of mutations in SLC26A4.

Even though the genetics of EVA are very complex, we have been able to identify some of its associated genetic mutations. One of the genes that has been repeatedly identified is called "SLC26A4", which codes for a protein called "pendrin". We have two copies of every gene, one from the mother and the other from the father, so we can have zero, one, or two mutated copies of SLC26A4. This study identified that EVA patients with zero SLC26A4 mutations have a pure-tone average of 62.6 dB, people with one SLC26A4 mutation have a pure-tone average of 52.9 dB, and people with two SLC26A4 mutations have a pure-tone average of 88.1 dB. Notably, they did not find any association between the number of copies and hearing loss progression.

Enlargement of the vestibular aqueduct (EVA) is one of the most common congenital malformations in pediatric patients presenting with sensorineural or mixed hearing loss. The relationship between vestibular aqueduct (VA) morphology and hearing loss across sex is not well characterized. This study assesses VA morphology and frequency-specific hearing thresholds with sex as the primary predictor of interest.

https://pubmed.ncbi.nlm.nih.gov/31060752/

Study to reveal hearing loss patterns in patients with enlarged vestibular aqueduct (EVA) syndrome according to demographic and clinical characteristics.

https://pubmed.ncbi.nlm.nih.gov/35276529/

This paper examines the relationship between diameter of VA and degree of air bone gap on audiometric testing. 98 ears in 49 patients with Pendred syndrome were studied by measuring the VA at the fundus, midpoint, and porous width and correlating with air bone gap. They found that patients with an air bone gap have larger diameters of the VA. The hypothesis and conclusion were that an EVA introduces a third mobile window into the inner ear, resulting in the low frequency air-bone gap.

Enlarged vestibular aqueduct (EVA) is a congenital condition that can lead to various outcomes in pediatric patients including hearing loss and vestibular dysfunction. Our goal was to critically appraise the literature on the proportion of patients with EVA who report vestibular dysfunction, determine relevant risk factors for the development of these symptoms, and describe vestibular tests and interventions used to improve outcomes.

https://pubmed.ncbi.nlm.nih.gov/34397103/

The title of this article begins with “vestibular pathology”, which means any disease or problem associated with the balance organs of the inner ear. Because EVA is an inner ear malformation, it follows that there might also be issues with the balance sensors of the inner ear.

This is a strong study because the authors decided to test each of the patients specifically for research purposes before any data was collected (this is called “prospective”) instead of relying on medical record information. The authors found that 24 of 27 patients with EVA showed signs of balance problems, and that vestibular aqueduct width was related to the extent of balance problems.

This study examines the effects of EVA on the vestibular system in patients with EVA. A prospective, cross-sectional study of a cohort from 1999 to 2013. In total, 106 patients with unilateral or bilateral EVA, participated in a study of the clinical and molecular aspects of EVA. Clinical history was ascertained with respect to the presence or absence of various vestibular signs and symptoms and history of head trauma. Videonystagmography (VNG), cervical vestibular evoked myogenic potential (cVEMP), and rotational vestibular testing (RVT) were performed to assess the vestibular function. Of the patients with EVA, 45% had vestibular signs and symptoms, and 44% of tested patients had abnormal VNG test results. An increased number of vestibular signs and symptoms was correlated with the presence of bilateral EVA (P = .008) and a history of head injury (P < .001). Abnormal VNG results also correlated with a history of head injury (P = .018). The study concluded that vestibular dysfunction is common in patients with EVA. However, not all patients with vestibular signs and symptoms have abnormal vestibular test results. Clinicians should be aware of the high prevalence of vestibular dysfunction in patients with EVA.

This study reports that people with bilateral EVA have abnormal balance sensation test results. The authors explain that there is too much excitability in one area of the inner ear (called otolithic organs) and not enough excitability in another area (called the semicircular canals). Either one of these dysfunctional sensory organs could contribute to balance issues, so this article is particularly important because it helps characterize the specific issues faced by people with EVA.