Vestibular Pathology in Children With Enlarged Vestibular Aqueduct

Transcription

1 The Laryngoscope VC 2016 The American Laryngological, Rhinological and Otological Society, Inc. Vestibular Pathology in Children With Enlarged Vestibular Aqueduct Christina J. Yang, MD; Violette Lavender, AuD; Jareen K. Meinzen-Derr, PhD; Aliza P. Cohen, MA; Mostafa Youssif, MD, PhD; Micheal Castiglione, AuD; Vairavan Manickam, MD; Katheryn R. Bachmann, PhD; John H. Greinwald, MD 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 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 and P 5.032, respectively). Also, high-frequency pure tone average (HFPTA) correlated with unilateral weakness (P 5.002). 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. Key Words: Enlarged vestibular aqueduct, cvemp, vertigo, vestibulopathy, vestibular testing. Level of Evidence: 2b. Laryngoscope, 126: , 2016 INTRODUCTION Enlarged vestibular aqueduct (EVA) is the most common abnormal radiologic finding in children with sensorineural hearing loss (SNHL). First described by Valvassori and Clemis, 1 this condition is defined as a Additional Supporting Information may be found in the online version of this article. From the Department of Otorhinolaryngology Head and Neck Surgery, Montefiore Medical Center (C.J.Y.), Bronx, New York; the Division of Audiology (V.L., M.C., K.R.B.); the Division of Pediatric Otolaryngology Head and Neck Surgery (J.K.M-D. A.P.C., J.H.G.); the Division of Biostatistics and Epidemiology (J.K.M-D.), Cincinnati Children s Hospital Medical Center; the Department of Otolaryngology Head and Neck Surgery, University of Cincinnati College of Medicine (J.H.G.), Cincinnati, Ohio; the Department of Otolaryngology Head and Neck Surgery, Geisinger Medical Center (V.M.), Danville, Pennsylvania, U.S.A.; and the Department of Otolaryngology, Sohag University Hospital (M.Y.), Sohag, Egypt Editor s Note: This Manuscript was accepted for publication January 5, Presented at the American Society of Pediatric Otolaryngology 2014 Spring Meeting at COSM; Las Vegas, Nevada, U.S.A., May 14 18, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to John H. Greinwald, MD, FAAP, The Ear and Hearing Center, Division of Pediatric Otolaryngology Head and Neck Surgery, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC 2018, Cincinnati, OH john.greinwald@ cchmc.org DOI: /lary vestibular aqueduct that is 2.0 mm at the operculum and/or 1.0 mm at the midpoint. 2 The otologic EVA phenotype is variable, associated with fluctuating and progressive sensorineural hearing loss, mixed hearing loss, and balance disorders. 3 9 Previous research 10 has shown a linear relationship between EVA width and progressive SNHL. Also, patients with bilateral EVA and SLC26A4 mutations have been shown to have a higher rate of SNHL progression than patients with no mutations. 8 Additionally, research indicates that unilateral EVA is not a strictly unilateral process because hearing loss and vestibular hypofunction may be present on the side contralateral to a unilateral EVA. 11,12 Literature pertaining to vestibular testing and symptoms in patients with EVA is limited. Specifically, in a retrospective study of both adults (n 5 11) and children (n 5 21) with EVA before and after cochlear implantation, authors noted preoperative vestibular symptoms (imbalance, vertigo, and/or motor delay) in approximately 46% and 48% of adult and pediatric patients, respectively. 13 Another retrospective study (n 5 17) of both adults and children with EVA 11 found that 87% of patients who underwent vestibular function tests exhibited marked vestibular weakness, although only 47% complained of vestibular symptoms. Authors of this study reported that there was no direct correlation between the side of the vestibular weakness and the

2 side of EVA. In the only study to date focused specifically on children (mean age 8.2), Zhou and Gopen 14 reported low cervical vestibular-evoked myogenic potential (cvemp) thresholds and high amplitudes in 25 children with EVA. Zalewski et al. 15 recently reported a high prevalence of vestibular dysfunction in a prospective study of 106 adult and pediatric patients with EVA. 15 Authors of this study reported both a high rate of vestibular signs and symptoms (45% overall, including a 23% prevalence of vertigo) and a high rate of abnormal vestibular test results (abnormal video nystagmography in 44% of patients). Of note, they found that vestibular signs and symptoms did not correlate with abnormal vestibular test results. However, the vestibular tests offered were not consistently performed among patients, varying by patient availability and tolerance, and the pediatric subset of patients was not specifically described. In view of these collective findings, we hypothesized that children with EVA would have a high rate of vestibular pathology. The objectives of our study were to establish the prevalence of abnormal vestibular test findings in children with EVA and determine if these findings correlate with clinical symptoms, radiographic findings (EVA size and laterality), audiometric findings, and genetic testing in this patient population. MATERIALS AND METHODS Children 3 to 12 years of age with SNHL and imaging findings consistent with unilateral or bilateral EVA 10 were sequentially enrolled from June 2009 to June Participation in the study also required a complete audiometric assessment and at least 3 months of audiometric follow-up data. Exclusion criteria included temporal bone dysmorphology that would prevent measurements, aural atresia, known non- SLC26A4-associated syndromic hearing loss, documented ototoxicity, a history of temporal bone fractures, meningitis, hydrocephalus with a shunt, autoimmune inner ear disease, auditory neuropathy, or middle ear effusion. cvemp and air caloric testing results were excluded in the case of tympanic membrane perforations. Demographic data, temporal bone measurements, genetic test results, and audiometric data were obtained for all study participants. If the most recent audiogram was performed more than 3 months prior to study enrollment, it was repeated. A questionnaire (Fig. 1) was administered to parents/caregivers to obtain information regarding their child s clinical history, including vestibular symptoms and age at which they began walking. Vestibular testing consisted of cvemp, posturography, rotational chair, and calorics. This study was approved by our institutional review board and was in compliance with Health Insurance Portability and Accountability Act of 1996 regulations. Audiometric Data A pure tone average (PTA) for each ear was derived by averaging the audiometric findings at 500; 1,000; 2,000; and 4,000 Hz on both the initial and most recent audiometric evaluations. A high-frequency PTA (HFPTA) was also derived for each ear by averaging the audiometric findings at 4,000; 6,000; and 8,000 Hz. A speech reception threshold (SRT), defined as Fig. 1. Balance questionnaire. DOB 5 date of birth. the decibel level at which 50% of spondee words were repeated correctly by the patient, was also derived for each ear. Progressive hearing loss was defined as an increase of 10 db in PTA over a minimum 3-month follow-up period. Ears with an initial PTA 95 db were eliminated from further analysis with regard to progressive SNHL. Progressive hearing loss was evaluated as the absolute change in PTA values, as well as the rate of change in PTA (in db loss per year), which takes into account time between visits. A mixed hearing loss was considered present in ears with normal tympanograms when there was a difference > 10 db between air conduction and bone conduction scores at one or more frequencies other than 250 Hz. Temporal Bone Computed Tomography Analysis All studies were performed for clinical diagnosis using a standard temporal bone protocol with contiguous 0.6- to 1-mm scan slices or 1- to 1.25-mm scan slices (per radiologic technology available at our institution at the time of diagnosis). Measurement of the various structures of the temporal bone seen on computed tomography (CT) scans was carried out according to a previously published algorithm. 2,10 Briefly, the width of the aqueduct was measured at both the operculum (a line perpendicular to the posterior surface of the petrous pyramid going to the most lateral or posterolateral pixel in the medial wall of the operculum) and at the midpoint between the coronal plane of the operculum and the coronal plane of the posterior wall of the crus commune or upper vestibule. The vestibular aqueduct was considered enlarged when its width exceeded the 97.5th percentile of normal temporal bones at either the operculum or the midpoint (1.9 mm and.9 mm, respectively). Abnormalities of the cochlea, vestibule, and semicircular canals were also reviewed on CT scan images. Genetic Testing Genomic DNA was isolated from blood and buccal swab tissues using the Puregene DNA purification kit (Gentra Systems, Minneapolis, MN) or the Roche MagA Pure Compact system (Roche Diagnostics Corporation, Indianapolis, IN) according to the manufacturers instructions. Coding exons and 2345

3 at least 50 base pairs of the adjacent intronic regions of the GJB2 (NC_ and NM_86849), MTRNR1 (NC_001807), and SLC26A4 (NC_ and NM_000441) genes were amplified by polymerase chain reaction (PCR), followed by bidirectional sequencing using the BigDye Terminator Cycle Sequencing Kit (Applied Biosystems by Life Technologies, Foster City, CA). Sequencing products were analyzed using the ABI Prism 3730 Capillary Sequence Detection System (Applied Biosystems by Life Technologies), and raw data were obtained and compared to the published consensus sequences using Sequencher 4.8 (Gene Codes Corporation, Ann Arbor, MI) sequencing analysis software. Vestibular Testing All study participants underwent vestibular testing at our pediatric vestibular laboratory. Among the vestibular tests in our laboratory, only posturography (the Sensory Organization Test [SOT]) using the SMART Equitest System (Neurocom, a division of Natus Medical Incorporated, San Carlos, CA) produces computer-generated results based upon published pediatric norms. 16 Therefore, our pediatric vestibular laboratory set out to establish these normative values for cvemp, rotational chair, and caloric testing as part of a concurrent but separate study of subjects aged 3 to 12 years without hearing loss (Appendix ). Cervical Vestibular-Evoked Myogenic Potentials cvemps were recorded with the Intelligent Hearing Systems SmartEP-evoked potential system (Intelligent Hearing Systems, Miami, FL) using an air-conducted, 500-Hz tone burst stimulus delivered monaurally via an ER-3A insert earphone (Etymotic Research, Elk Grove Village, IL) at a rate of 5.1 per second. Following skin preparation, the noninverting surface electrode was placed over the middle of the sternocleidomastoid (SCM) muscle, the inverting electrode was placed at the sternoclavicular junction, and the ground electrode was placed on the forehead. Children were then instructed to contract the SCM via head rotation in the sitting position or to lay supine at a 20- degree angle and contract the SCM via head elevation. Adequate SCM contraction was verified with a manufacturersupplied electromyogenic (EMG) contraction feedback device (Intelligent Hearing Systems, Miami, FL). This device was set up to allow children to view an animated cartoon if they were holding the SCM contraction between 50 lv and 150 lv. If the EMG level was below 50 lv or above 150 lv, the cartoon would pause, and response averaging would stop until the contraction returned to the desired EMG level. A 500-Hz tone burst stimulus was presented to each ear initially at an intensity level of 107 db hearing level (HL). Threshold was defined as the lowest intensity level at which the cvemp response could be visually identified and replicated. Posturography The SOT was administered to each study participant using the SMART Equitest System (Neurocom, a division of Natus Medical Incorporated, San Carlos, CA) to obtain an objective measure of postural control. The SOT assesses the patient s ability to effectively use visual, vestibular, and somatosensory input to maintain balance in six different conditions with varied sway referencing of the support or visual surround. Participants were fitted with a safety vest and harness and were asked to stand quietly on the sway referenced platform. Under condition 1, when participants stood on a fixed platform with their eyes open, all three sensory systems were operational and a baseline measure of stability was obtained. Condition 2 was the same as condition 1, except that participants had their eyes closed. Under condition 3, participants were in the same position as for condition 1, but the visual surround moved to track their sway. Under condition 4, participants stood with their eyes open and the visual surround fixed, but the platform moved in response to their sway. Condition 5 was identical to condition 4, except that the eyes were closed. Condition 6 was the same as condition 4, except that the visual surround moved in response to the participants sway. Cartoon stickers were used to help them maintain a forward gaze. A blindfold was used for younger patients who were unable to keep their eyes closed when necessary for testing. At least two trials were analyzed for each condition. Results were computer-generated and based on published norms for children ages 3 to 15 years. 16 Rotational Chair Sinusoidal harmonic acceleration testing was carried out via an enclosed motorized chair (Micromedical Technologies, Inc., Chatham, IL). Each participant was seated in a chair that moved in a sinusoidal pattern to each direction. The principle of rotational testing is that a stimulus applied to the chair would be the same as that applied to the head. Thus, the head was secured to the chair with a hook-and-loop strap. In order for the smaller children to reach the head restraint, a car booster seat was used to raise them up to the level of the head restraint. In addition, specially fitted pediatric goggles (with a monocular video camera) manufactured by Micromedical Technologies, Inc., were used. The testing protocol included one to two trials at each of the test frequencies, which included 0.02, 0.04, 0.08, 0.16, 0.32, and 0.64 Hz. Abnormal results in gain, phase, or symmetry at two consecutive test frequencies defined an abnormal test. Caloric Testing Bithermal and alternating open loop water caloric irrigations were completed for each participant using our pediatric balance laboratory protocol (warm water temperature 428C, cool water temperature 308C, 240 ml/40 sec). Our laboratory s normative cutoff values were 21% for unilateral weakness and 29% for directional preponderance (Appendix). Statistical Analysis Data distributions were reported using means with standard deviations for continuous data and frequencies with percentages for categorical data. Spearman correlation coefficients were used to evaluate the relationship between vestibular test findings (as continuous variables) with continuous clinical factors (i.e., EVA size, audiometric findings). Point biserial correlations (r pb ) were used to examine the relationship between vestibular test findings (as continuous variables) with dichotomous or discrete factors, such as clinical symptoms, and EVA laterality. For all analyses, a P value.05 was considered significant. All analyses were performed using SAS for Windows 9.3 (SAS Institute Inc., Cary, NC). RESULTS Twenty-seven patients (13 female) with a mean age of 9.2 years were enrolled in and completed the study. Of these patients, 37% had unilateral EVA and 63% had bilateral EVA. Twenty-two percent reported vertigo and 37% started walking later than 15 months of age. Thirty 2346

4 TABLE I. Clinical, Audiometric, Genetic, and Radiographic Characteristics of 27 Patients With EVA. N 5 27 patients (54 ears) Mean age at time of study (SD) 9.2 yrs (2.3) Female 13 (48%) Reported vertigo 6 (22%) Mean age child first walked SD, range) 14.6 mos (2.6,11 18) Mean PTA in worse hearing ear (SD) 58.8 (26) Mean SRT in worse hearing ear (SD) 51.7 (27) Isolated high-frequency hearing loss 11 (41%) Unilateral hearing loss 8 (30%) Type of hearing loss (among 54 ears) SNHL 15 (28%) CHL 3 (6%) Mixed 28 (52%) Normal 8 (15%) Progressive hearing loss 9 (33%) SLC26A4 status 2 (7.4%) heterozygous 0 (0%) homozygous Bilateral EVA 17 (63%) VA size (including normal VA ears) Midpoint (SD, range) 1.6 mm (1.0, 0 5) Operculum (SD, range) 2.7 mm (1.6, 0 7) Cochlear dysplasia (%) 11 (41%) Followup time (initial to final audiograms, SD, range) 67.8 mos (36, 3 120) EVA 5 enlarged vestibular aqueduct; PTA: pure tone average; SD 5 standard deviation; SNHL; sensorineural hearing loss; CHL 5 conductive hearing loss; SRT 5 speech reception threshold; VA 5 vestibular aqueduct. percent had unilateral SNHL. The mean PTA in the worse hearing ear was 58.8 db HL (SD 26, range 7 110). Of 20 patients tested for SLC26A4 mutations, two were heterozygous and none were biallelic (Tables I and II). Eighty-nine percent of patients had at least one abnormal vestibular test result (Table II). Six had abnormal results on two tests, four had abnormal results on three tests, and one had abnormal results on all four tests. A breakdown by specific test showed that 15% had abnormal cvemp results, 63% had abnormal SOT results, 44% had abnormal rotational chair results, and 32% had abnormal caloric results. There was no significant correlation between vertigo or age at which walking began and EVA size, although age at walking was later in the EVA group than in controls (see Appendix Table I). In addition, there was no significant association between unilateral versus bilateral EVA and the presence of vertigo or late walking. There were no significant associations between the presence of cochlear dysplasia, the presence or severity of hearing loss, and vertigo. Finally, there was no correlation between sidedness of EVA laterality and vestibular test findings. There were no statistically significant correlations between absolute cvemp thresholds and amplitudes and age, clinical symptoms, audiometric, or radiographic findings (Table III). However, both average and larger operculum size were positively correlated with an abnormal cvemp study (r pb 5.47, P 5.017; r pb 5.50, P 5.01, respectively). Caloric findings were correlated with ear-specific audiometric and radiographic findings (Table IV). Larger midpoint and operculum size were positively correlated with directional preponderance (P and P 5.032, respectively). Also, greater HFPTA was positively correlated with unilateral weakness (P 5.002). Neither unilateral weakness nor directional preponderance was correlated with EVA laterality (P 5.19 for both). The SOT results (conditions 1, 2, and 3 and composite score) were correlated with age, and results indicated that younger patients were more likely to fall (Table V). Walking at a later age (in months) was significantly correlated with increased sway in condition 1 (r , P <.05). There was no significant correlation between vertigo and any of the SOT conditions. Although low gain on rotational chair testing was noted in six patients, there were no significant correlations between rotational chair results and clinical, audiometric, or radiographic findings. DISCUSSION The results of this study suggest that children with EVA often have abnormal vestibular pathology, as demonstrated by laboratory testing. Interestingly, however, the high prevalence of abnormal vestibular test findings in this patient population was not correlated with vestibular symptoms, except with regard to later age at walking and SOT findings. This disparity parallels the findings of Zalewski et al. 15 in their mixed adult and pediatric cohort and can be attributed to several possible scenarios. Firstly, children who experience subtle vestibular symptoms such as nystagmus, clumsiness, or lack of coordination may compensate for a chronic, earlyonset peripheral vestibular deficit. They also may be unable to describe subtle symptoms to their parents or physicians. As well, these symptoms may go unrecognized by parents and physicians. Particularly noteworthy, the lack of correlation between EVA laterality and abnormal vestibular test findings corroborates results of previous studies of EVA and audiometric findings 11,12 and supports our previously published finding 12 that children with unilateral EVA may have hearing loss in the opposite ear. As we noted in that study, laterality may not have as strong of an impact on test results as EVA size in that the definition of EVA is based on a macroscopic radiologic finding, whereas the clinical pathology of EVA is a microscopic or cellular problem. Both cvemp and caloric testing correlated with EVA size but not with the degree of hearing loss, as measured by PTA and SRT. Furthermore, EVA size may have independent effects on hearing and balance. 2347

5 TABLE II. Demographic, Clinical, Audiometric, and Genetic Characteristics and Vestibular Test Findings for 27 Patients With EVA. Patient No. /Sex/ Age (y) PTA R PTA L Side of EVA Progressive HL SLC26A4 Status Walking Age (mo) Vertigo cvemp Posturography (SOT) Rotational Chair Caloric Testing 1/F/ Bilat No 2/2 12 No Abn Abn Wnl Wnl 2/M/ Bilat No 2/2 17 No Wnl Abn Wnl Wnl 3/M/ Bilat Yes Not tested 17 No Wnl Wnl Low gain Missed 4/M/ Bilat Yes 2/2 15 No Wnl Abn Wnl Wnl 5/F/ Bilat No 2/2 13 No Wnl Abn Wnl Wnl 6/F/ Bilat No 2/2 14 Yes Wnl Abn Wnl Wnl 7/F/ Bilat No 2/2 18 No Abn Wnl Wnl Wnl 8/F/ Bilat No 1/2 12 No Wnl Wnl Wnl 52% UW R 9/M/ L No 2/2 12 No Abn Abn Wnl Wnl 10/M/ Bilat Yes Not tested 18 No Wnl Abn High gain, phase lead Wnl 11/F/ L Yes Not tested 15 No Wnl Wnl High gain Wnl 12/M/ R No 2/2 11 No Wnl Wnl Wnl Missed 13/M/ Bilat No 2/2 18 No Wnl Abn Wnl 25% UW L 14/M/ Bilat Yes Not tested 12 Yes * Wnl Wnl * 15/F/ Bilat No 1/2 16 No Abn Abn CW, phase lead 63% UW L 16/M/ L No 2/2 17 Yes Wnl Abn CCW Wnl 17/F/ Bilat Yes Not tested 11 No Wnl Abn Wnl Wnl 18/F/ Bilat No 2/2 15 No Wnl Abn Wnl Wnl 19/F/ L Yes 2/2 11 No Wnl Wnl Wnl 25% UW L 20/M/ L Yes 2/2 12 No Wnl Abn High gain 48% UW L 21/M/ R No Not tested 17 No Wnl Abn CCW 28% UW R 22/F/ R No 2/2 13 No Wnl Wnl Wnl Wnl 23/F/ Bilat Yes 2/2 15 No Wnl Abn Phase lead 25% UW L 24/M/ L No 2/2 20 Yes Wnl Wnl Ccw 31% DP R 25/M/ R No 2/2 12 No Wnl Abn Low gain Wnl 26/F/ Bilat No Not tested 13 Yes Wnl Wnl Low gain Wnl 27/M/ Bilat No 2/2 18 Yes Wnl Abn Low gain Wnl *cvemp and air calorics excluded: patient 14 had dry perforations in both ears. EVA 5 enlarged vestibular aqueduct; Abn 5 abnormal; Bilat 5 bilateral; CCW 5 asymmetry with counterclockwise weakness; CW 5 asymmetry with clockwise weakness; cvemp 5 cervical vestibular-evoked myogenic potentials; DP 5 directional preponderance; L 5 left; PTA 5 pure tone average; R 5 right; SOT 5 sensory organization testing; UW 5 unilateral weakness; Wnl 5 within normal limits. TABLE III. First-Order Spearman Correlations With cvemp Results (ear-specific) in 27 Patients With EVA. Threshold* Amplitude Rho P value Rho P value Age Reported vertigo Walking age PTA SRT HFPTA Midpoint size Operculum size *Patient 14 excluded for dry perforations in both ears. Point biserial correlation reported. cvemp 5 cervical vestibular-evoked myogenic potentials; EVA 5 enlarged vestibular aqueduct; HFPTA 5 high-frequency pure tone average. HFPTA correlated with unilateral caloric weakness (P 5.002). Moreover, this was the only audiometric parameter that was correlated with abnormal vestibular test findings. These results suggest that HFPTA may be a sensitive indicator of caloric weakness. We previously found that HFPTA correlated independently with EVA size, 12 suggesting that patients with larger EVA and a high-frequency hearing loss may be at higher risk of vestibulopathy. We hypothesize that this relationship may be due to the proximity of the basilar turn of the cochlea and the vestibular apparatus. Later walking age correlated with abnormal SOT results and also indicated that younger patients were more likely to fall. Given that this particular test stresses the sense of balance more so than static tests of vestibular function, such as cvemp and caloric testing, this finding is not surprising. Moreover, it underscores the importance of SOT testing in children suspected of 2348

6 TABLE IV. First-Order Spearman Correlations With Absolute Value Caloric Results (ear-specific side of weakness or directional preponderance) in 27 Patients With EVA. UW DP Rho P value Rho P value Age Reported vertigo* Walking age PTA SRT HFPTA Bilateral HL* Progressive HL* Midpoint size Operculum size *Point biserial correlation reported. DP 5 directional preponderance; EVA 5 enlarged vestibular aqueduct; HFPTA 5 high-frequency pure tone average; HL 5 hearing loss; SRT 5 speech reception threshold; UW 5 unilateral weakness. TABLE V. First-Order Spearman Correlations With Computerized Dynamic Posturography Results (Person-Specific) in 27 Patients With EVA. CDP1 CDP2 CDP3 CDP4 CDP5 CDP6 Composite Age * 0.41 Reported vertigo Walking age Average PTA Worse PTA Average SRT Worse SRT Bilateral HL Progressive HL Bilateral EVA Average midpoint * * Average operculum Larger midpoint * * Larger operculum Bold values indicate P <.05. *P.10 P 5.11 Point biserial correlation reported. CDP 5 computerized dynamic posturography; EVA 5 enlarged vestibular aqueduct; HL 5 hearing loss; PTA 5 pure tone average; SRT 5 speech reception threshold. having vestibular pathology. 6,13,14,16 22 Although the rotational chair is a commonly used vestibular test in children, we did not find a correlation between rotational chair test findings and clinical symptoms in our EVA patient population. All of our patients completed this study, demonstrating that vestibular tests can be universally applied and better tolerated than is commonly believed, even in patients as young as 3 years of age. This comprehensive application of the vestibular test battery distinguishes our study from previous studies of both adults and children with EVA. 11,13,15 Our study has several limitations. Although it is one of the largest pediatric prospective studies of vestibular findings in children with EVA, our small sample size may limit the generalizability of our findings. Additionally, patients with cochlear dysplasia and SLC26A4 mutations are underrepresented in our cohort. These two findings may be related because patients with EVA and SLC26A4 mutations have more severe temporal bone anomalies. 8 As well, there were no patients with homozygous SLC26A4 mutations. Although this may be due to sample size, it may also reflect the high prevalence of monoallelic SLC26A4 mutations in patients with nonsyndromic EVA. 23 CONCLUSION Although we found a high rate of vestibular pathology in children with EVA, the prevalence of vestibular symptoms in this patient population was not correlated with vestibular test findings. However, walking at an older age, larger midpoint and operculum sizes, as well as greater HFPTA 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. The lack of correlation between EVA laterality and abnormal vestibular test findings parallels audiometric findings reported in previous studies and additionally suggests that patients with unilateral EVA may have contralateral hearing loss. Further prospective longitudinal studies are needed to determine the relationship between abnormal vestibular tests and clinically significant vestibulopathy in children with EVA, which may have an impact on interventions such as cochlear implantation and vestibular rehabilitation therapy. BIBLIOGRAPHY 1. Valvassori GE, Clemis JD. The large vestibular aqueduct syndrome. Laryngoscope 1978;88: Vijayasekaran S, Halsted MJ, Boston M, et al. When is the vestibular aqueduct enlarged? A statistical analysis of the normative distribution of vestibular aqueduct size. Am J Neuroradiol 2007;28: Antonelli PJ, Nall AV, Lemmerling MM, et al. Hearing loss in children with cochlear modiolar defects and large vestibular aqueducts. Am J Otol 1998;19: Arcand P, Desrosiers M, Dube J, et al. The large vestibular aqueduct syndrome and sensorineural hearing loss in the pediatric population. J Otolaryngol 1991;20: Arjmand EM, Webber A. Audiometric findings in children with a large vestibular aqueduct. Arch Otolaryngol Head Neck Surg 2004;130: Jackler RJ, De La Cruz A. The large vestibular aqueduct syndrome. Laryngoscope 1989;99:

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