Air and bone-conducted vestibular evoked myogenic potentials in children with large vestibular aqueduct syndrome.

BACKGROUND: There are few studies focused on vestibular symptoms and function of the children with LVAS. OBJECTIVES: This study aimed to find the characteristics of air and bone-conducted VEMPs among children with LVAS, and to investigate the relationship between VEMPs and vestibular symptoms. MATERIAL AND METHODS: A total of 44 children with LVAS and 10 healthy children were recruited as the case group and control group. Air and bone-conducted VEMP were performed to the participants. RESULTS: For air-conducted measurement, there was elevated amplitude of cVEMP in case group than control group. There was no significant difference at oVEMP parameters between the case group and control group. For bone-conducted measurement, significantly longer P1 latency and shorter P1-N1 latency of cVEMP were observed among the case group; there were a series of changes in oVEMP parameters among the case group. Logistic regression model revealed that air-conducted oVEMP asymmetric ratio was valuable to predict vestibular symptoms' development among the kids with LVAS. CONCLUSION: Asymmetric ratio of oVEMP could be used as one predictor of developing vestibular symptoms of the children with LVAS. Applying bone-conducted VEMP as one alternative parameter of vestibular syndrome is novel and will certainly remain an area of continued investigation.

The biomechanical characteristics of human vestibular aqueduct: a numerical-based model construction and simulation.

Vestibular aqueduct is a precise structure embedded in the temporal bone and plays a key role in the physiological function of inner ear by maintaining the endolymphatic circulation and buffering the impact from intracranial pressure. Although the alterations on the morphology or volume of vestibular aqueduct result in variety of diseases, the approaches of evaluating the condition of vestibular aqueduct are still unsatisfing because the pathological sections utilized for the 3D construction model most likely undergoes morphological changes. In this study, the vestibular aqueduct images obtained by CT scanning were processed by finite element method to construct the 3D model. To assess if this numerical model reflects the actual biomechanical properties of vestibular aqueduct, the fluid-solid coupling calculation was applied to simulate the endolymphatic flow in the vestibular aqueduct. By measuring the dynamics of endolymphatic flow, and the pressure and displacement on round membrane under external pressure, we found the numerical 3D model recapitulated the biomechanical characteristics of the real vestibular aqueduct. In summary, our approach of 3D model construction for vestibular aqueduct will provide a powerful method for the research of vestibular aqueduct-related diseases.

Vestibular modulation of skin sympathetic nerve activity in sopite syndrome induced by low-frequency sinusoidal motion.

Sopite syndrome, centered around the drowsiness, lethargy, and irritability associated with motion sickness, can be induced by exposure to low-frequency motion. It is known that the vestibular apparatus plays an important role in the pathogenesis of motion sickness, which features several autonomic responses, and we have previously documented increased vestibular modulation of skin sympathetic nerve activity (SSNA) and an increase in skin blood flow associated with nausea. Here, we assessed whether imperceptibly slow sinusoidal motion, sufficient to induce sopite syndrome but not nausea, also modulates SSNA and skin blood flow. Participants were seated upright and exposed to a randomized set of sinusoidal linear accelerations, ranging from 0.03 Hz at 0.5 mG to 0.2 Hz at 5 mG, via a motorized platform. At all frequencies vestibular modulation was greater than the cardiac modulation of SSNA, but cardiac modulation and skin blood flow were both significantly lower during the motion than at baseline. We conclude that sopite syndrome is associated with a marked modulation of sympathetic outflow to the skin and cutaneous vasoconstriction.NEW & NOTEWORTHY Little is known about the autonomic consequences of sopite syndrome-the drowsiness that can be induced by low-amplitude cyclic motion. We recorded skin sympathetic nerve activity (SSNA) in seated participants exposed to slow sinusoidal linear acceleration (0.03-0.2 Hz), which preferentially activates hair cells in the utricular part of the otolithic organs, at amplitudes that generated no sensations of motion. At all frequencies, there was a clear vestibular modulation of SSNA and cutaneous vasoconstriction.

Grades of hearing loss affect the presence of acoustically evoked short latency negative responses in children with large vestibular aqueduct syndrome.

OBJECTIVES: We aimed to investigate the relationship between grades of hearing loss and the presence of acoustically evoked short latency negative response (ASNR) in children with large vestibular aqueduct syndrome (LVAS), so as to enhance the reference value of ASNR for the diagnosis of LVAS in children. METHODS: Two hundred sixteen ears from 108 patients (aged 4-90 months) diagnosed with bilateral LVAS, with slight to profound hearing loss, were enrolled in the present study from January 2012 to December 2018. All of the cases were diagnosed with LVAS according to high-resolution computed tomography (HRCT) or magnetic resonance imaging (MRI) scans of the inner ears. The auditory brain stem response (ABR) tests were performed on these subjects with click stimulus (ck-ABR), and the ASNRs were detected based on the method recommended by previous studies. The degree of hearing loss for each ear was classified by the estimated pure-tone average (PTA) thresholds, which were calculated according to the ck-ABR thresholds. RESULTS: ASNRs were present in 40.7% (88/216) ears during ck-ABR tests. Both thresholds of ABR (Z = 2.977, p = 0.003) and estimated PTA (Z = 2.977, p = 0.003) were significantly higher in the ASNR absent group than in the ASNR present group. The frequency of not profound hearing impairment (≤80 dB HL) was much higher in the ASNR present group (44/88; 50%) than in the ASNR absent group (40/128; 31.3%) (χ2 = 7.714, p = 0.005). The results of the logistic regression model, adjusted by cases' age and gender, showed that compared with those ears with profound hearing impairment (>80 dB HL), the not profound impaired ears were associated with a 2.48-fold increased odds of recording ASNR presence in the ck-ABR test [odds ratio (OR) = 2.48, 95% confidence interval (CI): 1.38-4.46, p = 0.003]. CONCLUSIONS: Grades of hearing loss affect the presence of ASNR in children with LVAS, and manifesting as cases with not profound hearing impairment showed increased odds of recording ASNR in the ck-ABR test. Furthermore, more studies should be performed imperatively to determine the diagnosis value of ASNR in children with LVAS.

Biomechanical analysis of the clinical characteristics of enlarged vestibular aqueduct syndrome with Mondini malformation.

BACKGROUND: numerous researches on the pathological mechanism of Enlarged Vestibular Aqueduct (EVA) syndrome mainly focuses on the genetic characteristics of SLC26A4 gene and the function of its encoding protein, Pendrin. One of the limitations with these explanations is that it does not explain why cerebrospinal fluid pressure can affect clinical manifestations. OBJECTIVES: To establish a new approach to explain the clinical manifestations of EVA syndrome with biomechanical method. MATERIAL AND METHODS: 108 cases of EVA syndrome who received cochlear implantation were analyzed retrospectively. A cochlear model was built to reflect the differences of the structure in EVA syndrome with or without Mondini malformation. The CFD software was used to simulate and display the differences in mechanical pathogenic factors to which the model was subjected. RESULTS: EVA syndrome patients with Mondini malformation suffer more mechanical damage from the cerebrospinal fluid pressure due to their structural reason and their symptoms appear earlier and progress faster. CONCLUSIONS: Biomechanics is an important aspect of pathological mechanism of EVA syndrome, and it provides a new angle for clinical decision-making.

Enlarged vestibular aqueduct: Intraoperative electrocochleography findings during cochlear implantation.

Enlarged vestibular aqueduct (EVA) is the most frequent inner ear abnormality found on computed tomography in children with sensorineural hearing loss. The effects EVA abnormalities have on electrocochleography (ECochG) are unknown. Positive deflections in summation potential evoked by tone bursts were observed in 3/5 subjects, while a large negative deflection, similar to endolymphatic hydrops (EH), was observed for 2/5 subjects. The presence of an enlarged summation potential, with and without a compound action potential, was observed in response to a broadband click stimulus. Results suggest likely effects of a third window on ECochG responses and presence of EH in EVA.

Auditory Detection Thresholds and Cochlear Resistivity Differ Between Pediatric Cochlear Implant Listeners With Enlarged Vestibular Aqueduct and Those With Connexin-26 Mutations.

Purpose The goal of this study was to evaluate differences in the electrode-neuron interface as a function of hearing loss etiology in pediatric cochlear implant (CI) listeners with enlarged vestibular aqueduct (EVA) syndrome and in those with autosomal recessive connexin-26 mutations (DFNB1). Method Fifteen implanted ears (9 participants, 5 ears with EVA, 10 ears with DFNB1) were assessed. Single-channel auditory detection thresholds were measured using broad and spatially focused electrode configurations (steered quadrupolar; focusing coefficients = 0 and 0.9). Cochlear resistivity estimates were obtained via electrode impedances and electrical field imaging. Between-group differences were evaluated using linear mixed-effects models. Results Children with EVA had significantly higher auditory detection thresholds than children with DFNB1, irrespective of electrode configuration. Between-group differences in thresholds were more pronounced on apical electrodes than on basal electrodes. In the apex, electrode impedances and electrical field imaging values were higher for children with EVA than for those with DFNB1. Conclusions The electrode-neuron interface differs between pediatric CI listeners with DFNB1 and those with EVA. It is possible that optimal clinical interventions may depend, in part, on hearing loss etiology. Future investigations with large samples should investigate individualized CI programming strategies for listeners with EVA and DFNB1.

Inner ear pressure evaluation using wideband tympanometry in children with Large Vestibular Aqueduct Syndrome (LVAS): A pilot study.

OBJECTIVE: To investigate middle ear function in children with Large Vestibular Aqueduct Syndrome (LVAS) to explore the feasibility of measuring inner ear pressure using Wideband tympanometry (WBT). METHODS: 13 young children with LVAS were recruited. WBT and other audiological measurements i.e., Auditory Steady State Response (ASSR), Auditory Brain Stem Response (ABR), and Distorted Product Otoacoustic Emissions (DPOAE) were performed. Absorbance under ambient and peak pressure were compared with normative data, and analyzed using a one sample t-test. RESULTS: Average absorbance in children with LVAS was significantly lower than normative data under ambient pressure at 1000, 1189, 1296, 2000 Hz and 4000 Hz. Absorbance under peak pressure was also significantly lower at 707, 794, 917, 1000, 1189, 1297, 1498 and 2000 Hz. However, absorbance was higher than standard values above 4000 Hz under ambient and peak pressure. It was also higher under ambient pressure at frequencies below 500 Hz. CONCLUSION: The special characteristics of middle ear function found in children with Large Vestibular Aqueduct Syndrome (LVAS) indicate that WBT offers a sensitive and non-invasive method to evaluate inner ear pressure indirectly.

[Imaging characteristics of patients with large vestibular aqueduct syndrome and its relationship with the acoustically evoked short latency negative response].

Objective: To explore the imaging characteristics of large vestibular aqueduct syndrome (LVAS) patients and their relationship with the acoustically evoked short latency negative response (ANSR), so as to provide reference for the diagnosis of LVAS. Methods: Clinical data of 174 patients(334 ears) with LVAS diagnosed and treated by the Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Guangxi Medical University, from October 2009 to December 2017 were retrospectively analyzed, including 117 males and 57 females, aged from 5 months to 47 years old, with the median age of 4 years and 4 months. ABR and imaging data of patients were collected. Midpoint diameter and the outlet diameter of the vestibular aqueduct were measured on CT images, the midpoint diameter of the intraosseous parts and the extraosseous parts of enlarged endolymphatic sac(EES) were measured on MRI images. The correlation between the above measurements was analyzed by Pearson test using SPSS 17.0. According to whether ASNR was detected in ABR, the above data were divided into two groups, and the differences of the above imaging measurements were compared by the Independent-Sample Test. Results: The average midpoint diameter of the vestibular aqueduct was (1.87±0.58) mm (x±s, the following was the same), and the outlet diameter was (3.07±0.99) mm on CT; the average midpoint diameter of the intraosseous parts in enlarged endolymphatic sac(EES) was (2.39±1.37) mm, and the extraosseous parts was (2.50±2.18) mm on MRI. There was a correlation between the four measurements (P<0.05), among which the midpoint diameter of vestibular aqueduct was strongly positively correlated with the outlet diameter (r=0.760), and the remaining pairs were weakly correlated. ASNR was detected in 241 ears (72.16%,241/334) and undetected in 93 ears (27.84%, 93/334) of the 334 ears with LVAS. Midpoint diameter and the outlet diameter of the vestibular aqueduct in no ASNR group were smaller than the ASNR group, and the difference was statistically significant (t value was 2.814 and 2.754, P<0.05). There was no significant difference in the midpoint diameter of the intraosseous parts and the extraosseous parts of enlarged endolymphatic sac between the two groups, and the difference was no statistically significant(t value was 0.101 and 0.683, P>0.05). Conclusions: There is a strong positive correlation between the midpoint diameter of vestibular aqueduct and the outlet diameter in LVAS patients. There is a certain correlation between the size of vestibular aqueduct and the size of endolymphatic sac. The smaller the diameter of vestibular aqueduct, the lower the occurrence rate of ASNR.

Response of the inner ear to lipopolysaccharide introduced directly into scala media.

In an attempt to develop an animal model of immune mediated Meniere's disease, we have injected lipopolysaccharide (LPS) directly into scala media of guinea pigs and monitored functional and morphological changes over a period of 6 weeks. Depending on the concentration of LPS, changes ranged from moderate-to-severe hearing loss and endolymphatic hydrops with minimal cellular infiltrate or fibrosis, to dense cellular infiltration that filled the scalae. Interestingly, higher concentrations of LPS not only induced severe cellular infiltration, hydrops, and hearing loss, but also a substantial enlargement of the endolymphatic duct and sac. Moreover, LPS injections into perilymph failed to induce hydrops, yet still resulted in cellular infiltration and fibrosis in the cochlea. This suggests that chronic hydrops resulting from an immune challenge of the cochlea may not be due to blockage of the endolymphatic duct and sac, restricting fluid absorption. Furthermore, injecting antigen into endolymph may produce chronic immune-mediated hydrops, and provide a more promising animal model of Meniere's, although animals did not display signs of vestibular dysfunction, and the hearing loss was relatively severe.

[Research progress in imaging of large vestibular aqueduct syndrome].

Large vestibular aqueduct syndrome is one of the common non-syndromic hearing impairment. It is one of the most common inner ear abnormalities that cause hearing loss in children.The main performance is gradual or fluctuant hearing loss, from basic normal to extremely severe. Frequently seen in high frequencies hearing loss. The air-bone conduction gaps present in pure tone audiometry test with low frequencies. There were some inducements of intracranial pressure increases before premorbid. Some patients could be accompanied by vertigo or instability. So far, there was still no effective way to terminate the patient deafness progress.If there was no effective intervention,the speech developmental delay of children were an inevitable trend,greatly affect their normal social communication learning ability. So, early diagnosis was critical. Imaging examination was the golden criterion for the diagnosis of LAVS.Characteristic audiological performance and gene diagnosis can be the basis of the further diagnosed. Because the structure and anatomical location of vestibular aqueduct is small and deep, normal imaging examination is difficult to display its morphology and structure,so,for a long time, it did not work very well. Until the advent of High-resolution computed tomography and magnetic resonance imaging, there was a breakthrough and a deeper understanding of the fine structure with inner ear. We reviewed the latest progress of large vestibular aqueduct syndrome imaging studies.

The Giant Hand Illusion Experienced on a Simulator.

BACKGROUND: This paper discusses a special kind of a sensory illusion-the Giant Hand illusion-that was experienced during an exercise on a flight simulator equipped with a VR headset. In the first part we describe spatial disorientation and the function of the vestibular apparatus during flight and its consequences. In this part, the sensory illusion simulator used for the experiment is mentioned. In the second part we describe the simulator and test flight. In the third part we discuss data retrieved during simulator flights that are important for explaining the Giant Hand illusion. CASE REPORT: A well-trained pilot experienced the Giant Hand illusion while executing instrument flight rules flight on a simulator. The Giant Hand illusion was detected from the simulation data and confirmed by the pilot afterward. DISCUSSION: The Giant Hand illusion is a rare type of sensory illusion. The pilot falsely evaluated the situation as a malfunction of the aircraft controls. If the pilot had not been informed by the operator that he might have been influenced by the illusion, he would probably have crashed the simulated aircraft. An unrecognized Giant Hand illusion during a flight can lead to fatal consequences. This case report shows the symptoms and data that can be used for early recognition of this type of illusion.Frantis P, Petru A. The Giant Hand illusion experienced on a simulator. Aerosp Med Hum Perform. 2018; 89(6):557-562.

Vestibular Manifestations in Subjects With Enlarged Vestibular Aqueduct.

OBJECTIVE: To describe the results of a thorough evaluation in a large series of patients with an enlarged vestibular aqueduct (EVA), focusing on vestibular manifestations with etiological considerations. STUDY DESIGN: Retrospective chart review of patients with EVA. SETTING: Tertiary referral center. PATIENTS: A total of 22 EVA patients with a median age of 8 years (6 mo-35 yr) who underwent both audiovestibular and radiologic examinations. MAIN OUTCOME MEASURES: Patient demographics, radiologic findings, audiologic results, vestibular symptoms, findings of neurotologic examinations, and laboratory evaluations were collected and analyzed. Standard descriptive statistics were used to summarize patient characteristics. Subjects who had a history of vertigo attack were categorized as "vestibulopathy group," while subjects without any history of vertigo as "non-vestibulopathy group." RESULTS: Of the 41 ears included, 37 (90.2%) had hearing loss on initial audiometric evaluations. Among the 22 patients, 14 (63.6%) complained of dizziness. Of the 14 vertiginous patients, seven had recurrent episodes, five had a history of single attack, and two presented with postural imbalances. There were no significant differences between vestibulopathy and non-vestibulopathy groups with regard to the relationship between the development of vestibular symptoms and aqueductal size, hearing threshold, or age at first visit. Four of the 22 (18.2%) patients developed secondary benign paroxysmal positional vertigo (BPPV) and all patients complained of simultaneous decreases in hearing. CONCLUSIONS: Our results demonstrate that patients may develop vestibular symptoms during their clinical course, and all patients with an enlarged vestibular aqueduct should be cautioned regarding the potential development of vestibular pathology. Moreover, the non-negligible incidence of secondary BPPV mandates positional tests when evaluating EVA patients with vertigo.

Hearing eyeball and/or eyelid movements on the side of a unilateral superior semicircular canal dehiscence.

Hearing of eyeball movements has been reported in superior semicircular canal dehiscence (SSCD), but not hearing of eyelid movements. Our main objective was to report the hearing of eyeball and/or eyelid movements in unilateral SSCD. Our secondary objective was to access its specificity to SSCD and discuss the underlying mechanism. Six patients with SSCD who could hear their eyeball and/or eyelid movements were retrospectively reviewed. With the aim of comparisons, eight patients with an enlarged vestibular aqueduct (EVA), who share the same mechanism of an abnormal third window, were questioned on their ability to hear their eyeball and/or eyelid movements. Three patients with SSCD could hear both their eyeball and eyelid movements as a soft low-pitch friction sound. Two patients with SSCD could hear only their eyelid movements, one of whom after the surgery of a traumatic chronic subdural hematoma. The latter remarked that every gently tapping on the skin covering the burr-hole was heard in his dehiscent ear as the sound produced when banging on a drum, in keeping with a direct transmission of the sound to the inner ear via the cerebrospinal fluid. One patient with SSCD, who could hear only his eyeball movements, had other disabling symptoms deserving operation through a middle fossa approach with an immediate relief of his symptoms. None of the eight patients with EVA could hear his/her eyeball or eyelid movements. Hearing of eyeball and/or eyelid movements is highly suggestive of a SSCD and do not seem to occur in EVA. In case of radiological SSCD, clinicians should search for hearing of eyeball and/or eyelid movements providing arguments for a symptomatic dehiscence. The underlying mechanism is discussed particularly the role of a cerebrospinal fluid transmission.

Hearing Preservation During Cochlear Implantation and Electroacoustic Stimulation in Patients With SLC26A4 Mutations.

BACKGROUND AND OBJECTIVES: Patients with SCL26A4 mutations presenting with Mondini deformity and enlarged vestibular aqueduct (EVA) tend to have comparable residual hearing. Although cochlear implantation (CI) produces good results in this group, deterioration of residual hearing can be an adverse event after surgery due to accompanying cochlear malformation and perilymph leakage during cochleostomy. The purpose of this study was to investigate if CI in patients with SCL26A4 mutations via the round window (RW) approach could achieve preservation of residual hearing, and to evaluate their speech reception with electroacoustic stimulation (EAS). SUBJECTS AND METHODS: This is a retrospective chart review of eight patients with bilateral EVA, who were bi-allelic patients with SCL26A4 mutations. CI was performed in all patients by a single surgeon using the RW approach. Audiological results were compared before and after implantation. RESULTS: Additional hearing loss after CI was less than 10 dBHL in five out of eight patients. Average hearing deterioration after CI was 8.75 dB (range, 0-26). Six out of eight patients used EAS mode after CI. The acoustic stimulation frequency ranged from 271 to 438 Hz. Patients showed better speech recognition in quiet and in noise using EAS mode compared with electrical stimulation alone. CONCLUSIONS: Preservation of residual hearing could be achieved after CI in patients with the SLC26A4 mutation via the RW approach. For successful preservation of residual hearing, application of newly-developed soft electrode and meticulous surgical is necessary. Our study showed that patients with the SLC26A4 mutation can be good candidates for EAS surgery.

Contrasting results of tests of peripheral vestibular function in patients with bilateral large vestibular aqueduct syndrome.

OBJECTIVE: To analyze and summarize the effect of bilateral large vestibular aqueducts in peripheral vestibular organ function. METHODS: Eighteen patients with bilateral large vestibular aqueduct syndrome (LVAS; Study Group) and 18 healthy volunteers (Control Group) were investigated using audiometry, caloric test, sensory organization test (SOT), and vestibular-evoked myogenic potential (VEMP) tests. RESULTS: All 18 patients (36 ears) exhibited sensorineural hearing loss. For cervical VEMP (cVEMP), the Study Group showed lower thresholds (Study Group vs. CONTROL GROUP: 71.4vs. 75.3dBnHL; p=0.006), N1 latencies (24.1vs. 25.2ms; p=0.026) and shorter P1 (15.3vs. 16.6ms; p=0.003), and higher amplitudes (400.7vs. 247.2µV; p<0.001) than the Control Group. For ocular VEMP (oVEMP), the Study Group had lower thresholds (79.3vs. 81.8dBnHL; p=0.046) and higher amplitudes (40.6vs. 14.4µV; p<0.001) than the Control Group. Fourteen of 16 patients (87.5%) who completed caloric tests had abnormal results, and 10 of 18 patients (55.6%) exhibited abnormal results in SOTs. CONCLUSIONS: The hyperfunction of vestibular test in otolithic organs and the hypofunction of vestibular test in semicircular canals, as well as the dysfunction in the balance test were demonstrated in patients with LVAS. SIGNIFICANCE: Our findings can help clinicians gain a better understanding of the characteristics of vestibular organ function in patients with LVAS, which can facilitate optimal targeted treatment.

A nationwide study on enlargement of the vestibular aqueduct in Japan.

OBJECTIVE: To document the clinical features and associated pure-tone audiometry data in patients with enlargement of the vestibular aqueduct (EVA), and to identify risk factors for fluctuating hearing loss (HL) and vertigo/dizziness in EVA patients. METHODS: In this nationwide survey in Japan, a first survey sheet was mailed to 662 board-certified otolaryngology departments to identify the ones treating EVA patients. A second survey sheet, which contained solicited clinical information and the results of the hearing tests, was mailed to all facilities that reported treating EVA cases. We analyzed clinical information, including age at the time of the most recent evaluation, gender, EVA side, age at onset, initial symptoms, precipitating factors, and etiology from survey responses, and assessed 4-frequency (500, 1000, 2000, and 4000Hz) pure-tone average (PTA) from accompanying pure-tone audiometry data. A multivariate logistic regression analysis was utilized to identify the possible risk factors for fluctuating HL and vertigo/dizziness. RESULTS: In total, 513 hospitals (response rate, 77.5%) responded to the first survey, and 113 reported treating patients with EVA. Seventy-nine out of the 113 hospitals (response rate 69.9%) responded to the second survey, and the data of 380 EVA patients were registered and analyzed. Of the 380 patients, 221 (58.2%) were female, suggesting female preponderance. The patient age ranged from 0 to 73 years (mean, 16.7 years; median, 13 years; interquartile range, 6-24 years). EVA was bilateral in 91.1% of the patients (346/380). The most prevalent initial symptom was HL (341/380), followed by vertigo/dizziness/imbalance (34/380). Sudden HL occurred secondary to head trauma in 5.3% of the patients and upper respiratory infection in 5.0%. Pure-tone audiometry showed profound HL (PTA >91dB) in 316 (52.0%) of the 608 ears in the 304 patients tested, and asymmetric HL, defined as >10dB, in 147 (48.4%) of the 304 patients. The mean PTA was 83.7dB (median, 91.3dB; interquartile range, 71.3-103.8dB), and the severity in PTA did not correlate with age. Multivariate logistic regression identified age ≥10 years (compared to age of 0-9 years), bilateral HL (compared to unilateral HL/normal hearing), a history of head trauma, and Pendred syndrome (compared to the other EVA-associated disorders) as significant risk factors for fluctuating HL and/or vertigo/dizziness. CONCLUSION: The present nationwide survey of 380 EVA patients provided a more precise description of the clinical features, including risk factors for fluctuating HL and vertigo/dizziness.

Novel compound heterozygous mutations in SLC26A4 gene in a Chinese Han family with enlarged vestibular aqueduct.

OBJECTIVE: To identify the disease-related SLC26A4 mutants in a Chinese Han pedigree associated with Enlarged vestibular aqueduct (EVA). METHODS: EVA diagnosis was based on the family history, clinical examinations, systematically audiometric evaluations, high-resolution computed tomography (HRCT) of the temporal bone, and magnetic resonance imaging (MRI) of inner ear. Sanger sequencing and mutation analysis of the SLC26A4 gene were performed in all members of this family to identify the disease-related SLC26A4 mutants. Mutations in the SLC26A4 gene were compared with 200 ethnically matched control persons to exclude common polymorphism. RESULTS: All members in this family were negative for systemic and thyroid diseases. There were three subjects (I-2, II-2 and II-3) with bilateral sensorineural deafness since childhood. Temporal bone HRCT scans and inner ear MRI showed bilateral enlarged vestibular aqueduct with Mondini malformation in II-2 and II-3. A novel SLC26A4 splice-site mutation c.1001 + 5G > C was identified in compound heterozygosity with the mutation c.919-2A > G in the proband and in II-2. This novel compound heterozygote of two splice site mutations was not found in 200 normal hearing Chinese Han controls. CONCLUSIONS: A novel splice site mutation of c.1001 + 5G > C was identified, and the novel compound heterozygote of two splice site mutations, c.1001 + 5G > C and c.919-2A > G, in the SLC26A4 gene has been linked to hearing impairment in EVA patients.

Vestibular pathology in children with enlarged vestibular aqueduct.

OBJECTIVES/HYPOTHESIS: To establish the prevalence of abnormal vestibular test findings in children with enlarged vestibular aqueduct (EVA) and determine if these findings correlate with clinical symptoms, radiographic findings (EVA size and laterality), audiometric findings, and genetic testing in these patients. STUDY DESIGN: Prospective cohort. METHODS: Patients 3 to 12 years of age with hearing loss and imaging findings consistent with EVA treated at our tertiary care institution were sequentially enrolled from 2009 to 2011. The following six outcome measurements were analyzed: audiometric findings, EVA laterality, temporal bone measurements, genetic testing, vestibular testing (cervical-evoked myogenic potentials, posturography, rotational chair, and calorics), and vestibular symptoms. RESULTS: Twenty-seven patients with EVA (mean age 9.2 years, 48% female) were enrolled in and completed the study. Vertigo was reported in six patients. Twenty-four of 27 (89%) had at least one abnormal vestibular test result. Midpoint and operculum size correlated with directional preponderance (P = .042 and P = .032, respectively). Also, high-frequency pure tone average (HFPTA) correlated with unilateral weakness (P = .002). Walking at a later age correlated with abnormal posturography results. There was no correlation between EVA laterality and vestibular test findings. CONCLUSION: We found a high rate of vestibular pathology in children with EVA; however, the prevalence of abnormal vestibular test findings in this patient population was not correlated with vestibular symptoms. Enlarged vestibular aqueduct size, HFPTA, and walking at a later age were correlated with abnormal vestibular test findings. In view of these results, it may be prudent to consider vestibular testing in children with these clinical characteristics. LEVEL OF EVIDENCE: 2b. Laryngoscope, 126:2344-2350, 2016.

Cochlear implantation in patients with inner ear bone malformations with posterior labyrinth involvement: an exploratory study.

Inner ear bone malformations are one cause of profound sensorineural hearing loss. This investigation focused on those affecting the posterior labyrinth, especially enlarged vestibular aqueduct syndrome, which is associated with fluctuating and progressive hearing loss. The objectives of this study were to analyze the behavior of the electrical stimulation, auditory functionality and linguistic development in patients with inner ear malformations involving the posterior labyrinth. The study included ten patients undergoing cochlear implantation (cases: five with enlarged vestibular aqueduct, two with vestibular aqueduct stenosis/aplasia, and three with semicircular canal disorders). Post-implantation, data were gathered on the electrical stimulation threshold and maximum comfort levels and on the number of functioning electrodes. Evaluation of Auditory Responses to Speech (EARS) subtests were used to assess auditory functionality and language acquisition at 6, 12, and 24 months post-implantation. Results were compared with findings in a control group of 28 cochlear implantation patients without these malformations. No significant differences were found between case and control groups in electrical stimulation parameters; auditory functionality subtest scores were lower in cases than controls, although the difference was only statistically significant for some subtests. In conclusion, cochlear implantation patients with posterior labyrinth bone malformations and profound hearing loss, including those with enlarged vestibular aqueduct syndrome, showed no significant difference in electrical stimulation threshold with controls. Although some auditory functionality test results were lower in cases than in controls, cochlear implantation appears to be beneficial for all patients with these malformations.