Enlarged Vestibular Aqueduct: Review of Controversial Aspects

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1 The Laryngoscope VC 2011 The American Laryngological, Rhinological and Otological Society, Inc. Contemporary Review Enlarged Vestibular Aqueduct: Review of Controversial Aspects Quinton Gopen, MD; Guangwei Zhou, MD, ScD; Kenneth Whittemore, MD; Margaret Kenna, MD, MPH Objectives: To review the controversial aspects of the enlarged vestibular aqueduct syndrome. Study Design: Contemporary review. Methods: A literature search using the terms enlarged vestibular aqueduct and large vestibular aqueduct were used to generate the articles for review in this article. Results: The enlarged vestibular aqueduct is a condition causing variable auditory and vestibular dysfunction. Although it has been 32 years since Valvasorri and Clemis recognized the clinical importance of the enlarged vestibular aqueduct, many controversial aspects of the diagnosis remain. The topics reviewed in this discussion are as follows: size criteria for radiographic diagnosis, precipitating factors for hearing loss, corticosteroid treatment and sac surgery, conductive component to hearing loss, natural progression of hearing loss, correlations between aqueduct size and hearing loss, genetics, vestibular symptoms, and theories regarding mechanisms behind the symptoms. Conclusion: The enlarged vestibular aqueduct remains a controversial entity with variable presentation, progression, and prognosis. Key Words: Cranial base, otology, pediatric ears/otology, vestibular. Level of Evidence: 2a. Laryngoscope, 121: , 2011 INTRODUCTION The vestibular aqueduct is a temporal bone structure that runs from the vestibule to the posterior cranial fossa. It contains the endolymphatic duct, which terminates at the endolymphatic sac within the bony operculum. Both auditory and vestibular dysfunction have been associated with enlargement of the vestibular aqueduct. The enlarged vestibular aqueduct was first discovered by Mondini in 1791, during a temporal bone dissection. 1 Mondini described a specific cochlear malformation of incomplete cochlear partition (hypoplastic modiolus), short cochlear duct with flat cochlea, auditory and vestibular organs that were immature, a dilated vestibule, semicircular canals that were wide, small, or missing, an endolymphatic sac that was bulbous, and a large vestibular aqueduct. Instead of its usual 2.5 turns, the cochlea had 1.5 turns with an absent interscalar septum From the Division of Head and Neck Surgery (Q.G.), U.C.L.A. Medical Center, Los Angeles, California, U.S.A.; Department of Otolaryngology and Communication Enhancement (G.Z., K.W., M.K.), Children s Hospital Boston, Harvard Medical School, Boston, Masschausetts, U.S.A. Editor s Note: This Manuscript was accepted for publication May 10, The authors have no financial disclosures for this article. The authors have no conflicts of interest to disclose. Send correspondence to Dr. Quinton Gopen, Division of Head and Neck Surgery, U.C.L.A. Medical Center, 200 Medical Plaza, Suite 550, Los Angeles, CA qgopen@mednet.ucla.edu DOI: /lary between the middle and apical turn. Embryologically, this corresponds to arrest in development during the seventh week of gestation. Valvassori first reported Meniere s like symptoms in the presence of an enlarged vestibular aqueduct in Valvasori and Clemis 3 are credited with recognizing the clinical relationship between enlarged vestibular aqueducts and hearing loss in 1978 when they identified enlargement of the vestibular aqueduct in 50 cases out of 3,700 tomograms, or 1.4%. Of these 50 cases, most had congenital hearing loss and many had vestibular symptoms. The enlarged vestibular aqueducts in their study measured from mm in diameter. They considered a measurement greater than 1.5 mm in anterior posterior diameter as abnormally enlarged. Sixty percent had other structural anomalies, including an enlarged vestibule (14), an enlarged vestibule and semicircular canals (7), an enlarged vestibule and hypoplastic cochlea (4), and hypoplastic cochlea (4). In addition, the authors suspected many others had abnormalities below the level of resolution of the tomograms. In their series, the enlarged vestibular aqueducts were 2:1 bilateral to unilateral and 3:2 female to male. The enlarged vestibular aqueduct remains the most common inner ear anomaly found on radiographic evaluation of children with hearing loss. 4 The enlarged vestibular aqueduct syndrome is associated with Pendred s syndrome and with mutations in the SLC26A4 (PDS) gene. This gene encodes for pendrin, 1971

2 an important protein involved in the cellular transport of chloride, iodine, and bicarbonate anions. Mutations in SLC26A4 can cause Pendred s syndrome as well as nonsyndromic recessive deafness (DFNB4). Enlarged vestibular aqueducts have also been associated with distal renal tubular acidosis, 5,6 Waardenburg s syndrome, 7 X-linked congenital mixed deafness, 8,9 branchio-oto-renal syndrome, 10,11 otofaciocervical syndrome, 12 and Noonan s syndrome. 13,14 Since its initial discovery in 1791, many controversial aspects about the condition remain. This review attempts to summarize our current understanding of enlarged vestibular aqueduct syndrome as well as these controversial aspects. METHODS For this review, a literature search using pubmed was conducted using the key words large vestibular aqueduct and enlarged vestibular aqueduct. The search was limited to publications in English. Additional articles were also obtained from the references in any included studies. DISCUSSION Radiographic Size Criteria for Diagnosis The initial size criterion for the diagnosis of an enlarged vestibular aqueduct was put forth by Valvassori and Clemis 3 in their landmark paper in In this report, the bony vestibular aqueduct was considered enlarged if it was greater than 1.5 mm at the midpoint of its course from the vestibule to the posterior cranial fossa. Jackler 15 used the criteria for diagnosis of an enlarged vestibular aqueduct if the diameter was greater than 2 mm at its midpoint. Other investigators also used 2 mm at the aqueduct s midpoint, including Arcand and Levenson. 16,17 Okumura 18 defined the aqueduct as enlarged if it was greater than 4 mm at the operculum or if the distance between the vestibule and traceable part of the vestibular aqueduct nearest the vestibule was short, specifically less than 1 mm. Wilson s 19 definition compared the aqueduct to the posterior semicircular canal, and considered it enlarged if the diameter of the aqueduct at its midpoint was twice the diameter of the posterior semicircular canal. Most recently, the Cincinnati group advocated the criteria for enlargement be revised down to 0.9 mm at the midpoint or 1.9 mm at the operculum. Their rationale was based on a large series of patients without other identifiable causes for hearing loss. 20 They used this study as evidence that borderline patients without another explanation for their hearing loss do, in fact, have symptomatic enlarged vestibular aqueducts. In 2009, Dewan 21 reviewed 130 cochlear implant candidates and found that 16% had enlarged vestibular aqueducts based on the Valvasori criteria but 45% had enlarged vestibular aqueducts based on the Cincinnati criteria. This resulted in 70 ears that had previously unexplained hearing loss to subsequently be classified as having an enlarged vestibular aqueduct. In an attempt to define the spectrum of size for normal vestibular aqueducts, Vijayaserkaran et al. 22 in 2007 reviewed 73 CT scans of children without sensorineural hearing loss and found a range of mm at the midpoint and a range of mm at the operculum. They found that 95% of vestibular aqueducts were less than 0.9 mm at the midpoint and 1.9 mm at the operculum. They used these figures to support 0.9-mm midpoint and 1.9-mm operculum diameters as the threshold for the diagnosis of enlarged vestibular aqueduct. Again, however, this is an arbitrary supposition. In fact, this study can be interpreted in exactly the opposite way: specifically, that 5% of normal scans will have vestibular aqueducts that are greater than the Cincinnati criteria and be classified incorrectly. This further supports the notion of confirmatory functional testing whenever possible. Precipitating Factors for Hearing Loss Many investigators have noted that a small but significant fraction of enlarged vestibular aqueduct patients lose some or all of their hearing with certain events. The most widely reported precipitating event is head trauma, representing a small percentage in many series of patients with enlarged vestibular aqueducts (see Table I). The head trauma need not be severe. In addition to head trauma, some investigators have also linked barotrauma (including Valsalva), upper respiratory tract infections, high fevers, noise trauma, and physical exercise to hearing loss. For head trauma, by far the most commonly reported precipitator, the incidence was as high as 80% in one small study, but has a wide range of incidence in different reports. 23 Table I shows the different series with the incidence found in each patient population and the etiology reported. The natural history of the acute trauma induced hearing loss is quite variable, with some patients having full recovery while other patients have persistent hearing loss without improvement. This has significant implications for patient counseling. Some investigators recommend restricting activities, especially contact sports, to limit the risk of hearing loss associated with head trauma. 34 Although upper respiratory tract infections and high fevers are somewhat unavoidable, head trauma can be minimized by avoiding contact sports and barotrauma can be minimized by avoiding activities that might provoke a change in hearing, such as scuba diving, sneezing with the nose pinched closed, straining when going to the bathroom, weight lifting, and other similar activities. The discussion becomes even more complex when the enlarged vestibular aqueduct is bilateral, a common occurrence. Type of Hearing Loss The type of hearing loss in enlarged vestibular aqueduct syndrome remains a point of significant controversy. All three types of hearing loss (sensorineural, mixed, and conductive) have been reported in the condition. Pure conductive hearing loss is by far the least common type in all studies reported. Although some investigators describe sensorineural hearing loss in the majority of patients, some believe that nearly all patients with enlarged vestibular aqueduct have an air 1972

3 TABLE I. Review of Series Reporting Precipitating Factors Resulting in Hearing Loss in Enlarged Vestibular Aqueduct Patients. Study Year Patients in Series (Total) Patients with Loss from an Event (%) Etiology Levenson /12 (25) head trauma 1/12 (8.3) valsalva 1/12 (8.3) barotrauma Jackler /17 (11.8) head trauma Arcand /33 (3.0) head trauma Okumura /13 (53.8) head trauma, URI, or exercise Dahlen /21 (9.5) head trauma Antonelli /26 (11.5) valsalva 3/26 (11.5) head trauma Govaerts sometimes head trauma occurred Harker /5 (80.0) head trauma Mamikoglu case report head trauma Madden /77 (3.9) head trauma Lin /16 (18.8) head trauma 4/16 (25.0) URI Berrettini /17 (29.4) head trauma or other triggering event Colvin /27 (3.7) URI 1/27 (3.7) exercise 7/27 (25.9) head trauma Steinbach N/A noise trauma Grimmer /32 (6.3) barotrauma 3/32 (9.4) high fevers 6/32 (18.8) head trauma Ma /23 (21.7) head trauma Atkin /20 (15.0) head trauma bone gap, particularly at the lower frequencies Part of the explanation for discrepancies between studies may be improper or incomplete audiometric testing. 37 Specifically, many children are examined using ABR testing, which poses some difficulties in the assessment of the lowest frequencies with bone conduction and may lead to an overestimation of sensorineural hearing loss instead of mixed hearing loss in many cases. Furthermore, many cases have bilateral severe hearing loss, creating a masking dilemma that further confounds results. Table II summarizes the major studies reporting the type of hearing loss. Certainly numerous confounding factors make the data analysis difficult and varied. Some of the studies suffer from selection bias. Specifically, the study by Antonelli 25 required sensorineural hearing loss as a criteria for obtaining a computed tomography (CT) scan and entrance into their study. Similarly, Arjmand 41 required sensorineural hearing loss as a criteria for enrollment in study. Patients with enlarged vestibular aqueducts can have suprathreshold bone conduction responses, particularly at lower frequencies. Consequently, a patient could have an enlarged vestibular aqueduct with an air bone gap but without sensorineural hearing loss and would not be enrolled in many of the studies above, resulting in a selection bias against conductive hearing loss patients. Different size entrance criteria between studies as to what defines enlarged vestibular aqueduct may also play a role. In addition, some patients with enlarged vestibular aqueduct progress to profound hearing loss, making testing of bone conduction difficult or impossible. Such patients may not show an air bone gap when the ear becomes deaf, but would have demonstrated air bone gaps if tested earlier in the course of the condition. Hearing Loss Progression over Time This is certainly one of the most controversial aspects of the disorder. The spectrum of enlarged vestibular aqueduct hearing loss ranges from complete deafness in early childhood to stable hearing well into adult life. As the condition was identified just over 30 years ago, many patients older than that were not diagnosed with the condition. Furthermore, submillimeter CT and magnetic resonance (MR) imaging are now routinely used, but were not readily available in the 1970s. This certainly skews the population toward younger patients. As time goes forward, many of the major centers should have long-term data such that patients with the condition can be followed later in life yielding better long-term statistics. Currently, there is no valid method to predict what a patient s hearing will be in the years to come. To date, no study has associated either gender or bilaterality with hearing loss progression. Table III summarizes the studies that categorize the hearing loss into stable, fluctuating, and progressive. Some studies divide the categories into stable and not TABLE II. Series Reporting Hearing Loss by Type. Study Year Patients Ears SNHL (%) Mixed (%) CHL (%) Normal Hearing (%) Valvassori ? Emmett Jackler Antonelli Govaerts Nakashima Sato Madden * 0 Lai Arjmand Berrettini * 0 Colvin * 0 Zhou Reyes King ? *Represents combined mixed hearing loss and conductive hearing loss (not delineated seprately in these studies). SNHL ¼ sensorineural hearing loss. 1973

4 TABLE III. Hearing Loss Progression Over Time. Study Year Patients Ears Stable Fluctuating Progressive f/u Years Mean Valvassori ? Emmet * 2 days to 12 years Jackler Levenson Arcand * 4.0 Okumura * 1.4 Zalza l * 3.8 Antonelli Madden ? Arjmand ?? ? Lai *? Baerrettini ? Colvin Madden Grimmer ? Reyes Atkin *? King *Represents combined fluctuating and progressive hearing loss (not delineated separately in these studies). stable (combining fluctuating and progressive; see Table III). If mean follow-up was not provided but the range of follow-up was provided it is reported. If no mention of follow-up is given in the study, it is demarcated by a?. Again, the studies are confounded by different entrance criteria for each category. For example, how are patients that are deaf at their first visit categorized? In some ways they can be considered stable, as the hearing is not changing over time. Another interpretation would be they are progressive and just at the end stage of progression. What defines stable hearing? Some studies show a gradual hearing loss of around 4 db per year, such that small changes in hearing may be classified as stable by some and progressive by others. This might help explain the wide ranges reported. For example, stable hearing was as high as 83% and as low as 16%. The three longer term studies had somewhat similar results. Reyes with a 9.5-year mean follow-up found 47% of the ears were stable 42 and Colvin with a 9.7-year mean follow up found 30% of the ears to be stable. 29 Jackler, 15 with a 7.3-year mean follow-up had 35% of the ears stable. Certainly long-term follow-up is needed to sort out these differences with a more consistent categorization between centers. This notion is supported by the Zalzal study when groups were divided into less than 2 years and greater than 2 years, with a significant increase in the incidence of progression within the longer term group. 4 Steroid Treatment The idea that corticosteroid therapy could benefit patients with an enlarged vestibular aqueduct stemmed from patients who had a sudden sensorineural hearing loss. Corticosteroids are often used to treat idiopathic sudden sensorineural hearing loss. 44,45 Grimmer 46 studied the use of steroids in enlarged vestibular aqueduct patients retrospectively in a small cohort of 12 patients. He noted hearing improvement in four of five patients treated with corticosteroids but a lack of hearing improvement in six of seven patients that were not treated with steroids. He determined a prospective study with approximately 20 to 45 patients in each group would be required to prove statistical significance. Lin and coworkers, 28 in 2005, studied 16 children retrospectively with enlarged vestibular aqueducts and defined successful treatment if the hearing thresholds improved by 10 db at two frequencies. Seven children over 4.5 years had 13 episodes of hearing loss, with an 85% improvement rate. No control group was used in this study. This is quite problematic, as the natural history of thediseaseisknowntohaveahighincidenceofspontaneous recovery after fluctuations in hearing. To date, there have been no prospective trials of either systemic or intratympanic corticosteroid use in enlarged vestibular aqueduct patients who have fluctuating or progressive hearing loss. Endolymphatic Sac Surgery Endolymphatic sac surgery has been attempted to improve or even stabilize hearing in patients with enlarged vestibular aqueducts. In 1989, Jackler 15 reviewed this very supposition and concluded that endolymphatic sac shunt surgery is contraindicated in the disorder after four of seven patients he operated on had a significant early decline in hearing thresholds on postoperative follow-up evaluation. Welling, 46 in 1999, had similar results, performing endolymphatic sac occlusion on 10 patients, with 9 patients having some degree of additional haring loss after the procedure. 1974

5 The only study with favorable results was done by Wilson, 19 in 1997, when he reported a series of endolymphatic sac obliterations on seven children. He reported six of seven patients maintained stable hearing on longterm follow-up, between 6 months and 6 years. One patient had continued progression of their hearing loss, and no control groups were used in this small study. EVA Size Correlations with Hearing Loss There is some discrepancy as to whether the magnitude of the enlarged vestibular aqueduct plays a role in hearing loss severity or progression. Several studies have reviewed this topic with mixed results. Antonelli 25 found the amount of enlargement and morphology of the vestibular aqueduct correlated highly with the severity of hearing loss, but that the degree of modiolar deficiency did not correlate with hearing loss. Madden 7 found a correlation between vestibular aqueduct size at the operculum and progressive loss. Lai 40 showed the midpoint diameter and the diameter at the operculum of the enlarged vestibular aqueduct correlated with the frequency and severity of hearing loss fluctuations, but did not correlate with the progression of hearing. In contrast, most studies have not shown correlation between hearing loss and sac or duct size. 4,6,17,24,29,47 49 Naganawa, 50 in 2000, used 1.5 T T2-weighted MR sequences to quantify the volume of the vestibular aqueduct and sac, the area of the modiolus, the diameter of the duct and sac, and the signal intensity of the endolymphatic sac, and did not show any significant correlation with the degree of hearing loss. SLC26a4 (PDS) Gentotype Correlates with Hearing Loss and Enlarged Vestibular Aqueduct In 1896, Vaughn Pendred, 51 in the Lancet, described two Irish sisters with goiter and hearing loss. In 1927, Brain 52 described it as having autosomal recessive inheritance. In 1960, Fraser et al., 53 using the perchlorate discharge test, recognized the variability in the thyroid function in patients with Pendred syndrome. Then, several investigators, including Sheffield et al. (1996), 54 Gausden et al. (1997), 55 and Coucke et al. (1997) 56 linked the region for the PDS gene to 7q31. In 1997, Everett et al. 57 identified PDS, also called SLC26A4, as the gene causing Pendred syndrome. Abe et al. (1999) 58 noted patients with EVA and fluctuating sensorineural hearing loss had localization of the gene to 7q31, a region containing the Pendred syndrome gene. Finally, in 1999, Usami et al. 59 found that mutations in the PDS gene were associated with the presence of both syndromic (Pendred syndrome) and nonsyndromic (DFNB4) enlarged vestibular aqueducts. Some studies have correlated SLC26A4 mutations with a worse prognosis for hearing. In 2006, Albert 60 reported that biallelic mutations in SLC26A4 in nonsyndromic patients had more severe hearing loss and a higher likelihood of fluctuations when compared to enlarged vestibular aqueduct patients without SLC26A mutations. Another study by King, 43 in 2009, correlated a worse hearing prognosis with identification of the SLC26A4 genotype in patients with enlarged vestibular aqueducts. King did not find any correlation between cochlear anomalies and hearing loss. Madden 20 found a correlation between SLC26A4 mutations with wider aqueducts at the midpoint and more severe hearing loss. In opposition, however, both Reyes 42 and Jonard 61 recently have published studies that show no correlation between SLC26A4 gene mutations and hearing loss. Vestibular Symptoms Certainly, vestibular dysfunction has been correlated with the diagnosis of an enlarged vestibular aqueduct. Several case reports of children and adults with enlarged vestibular aqueducts and symptoms of vestibular dysfunction can be found The vestibular symptoms are typically dysequilibrium or epidosic vertigo attacks of variable length. Younger children may present with motor delays such as delayed ambulation and poor coordination. Interestingly, some of the reported series evaluating the frequency of vestibular dysfunction, either based on symptoms or abnormal testing, have revealed a wide disparity of results. The incidence of vestibular symptoms ranged from 0% to 100%, but this likely represents selection criteria bias for inclusion within each study. Comparison of these studies is difficult due to differences in age, variable lengths of follow-up, and different inclusion criteria. Okumura 18 stated that their study identified a higher incidence of vestibular symptoms due to a longer period of follow-up with a mean duration of 11 years. Grimmer s 47 study also found no statistical differences when comparing adult and pediatric rates of vestibular dysfunction. Many of the studies report vestibular symptoms but only performed selected vestibular testing. These studies are summarized in Table IV. Some of the inherent difficulties in establishing a frequency for vestibular symptoms in any study are the assessment of pediatric patients. Most studies have a majority of pediatric patients, some of whom are too young to report vestibular symptoms. Furthermore, pediatric patients are much more resilient in general to vestibular symptoms than adult patients, and may not report dysequilibrium or even milder forms of vertigo. If a child has severe vestibular loss from the condition in the perinatal period or early during development, they may display few vestibular symptoms later in life, as they will have compensated through development. Hypothesis for Etiology of Hearing Loss in Enlarged Vestibular Aqueduct Patients Many different theories as to how the enlarged vestibular aqueduct leads to hearing loss have been proposed. Some feel that the enlarged vestibular aqueduct is an epiphenomenon, with the true pathology being undetected at a molecular level. However, the theories proposed to date are listed below: 1. Back pressure/damaging pressure wave theories: Early on, Valvasori, 3 and more recently Riley 66 both 1975

6 Study Year Patients TABLE IV. Vestibular Symptoms and Testing. Vestibular Symptoms Vestibular Testing Valvassori %* 100% patients (6 patients tested) markedly decreased or absent vestibular functions tests Valvassori % vestibular function tests absent or markedly reduced in 80% of patients Emmett % ENG reduced in 53% of patients rotational chair with low-frequency phase lag 100% of patients and 57% of patients had directional preponderance Jackler % ENG in 2 patients one with direction changing nystagmus and normal ENG the other with no response but had no vestibular symptoms Schessel % reduced calorics 67% of patients Okumura % reduced calorics 100% of patients Okumura % none reported Antonelli % none reported Yetiser % 90% of patients with ENG reduced or no response Nakashima % VEMP with increased amplitude at reduced threshold in 92% of patients, absent in 8% of patients Oh % 1 patient: ENG normal, rotational chair testing normal 1 patient: no testing done 1 patient: ENG normal but rotational chair testing with decreased gain and increased phase lead Naganawa % no testing reported Madden % no testing reported Sheykholeslami % ENG normal (1 patient), VEMP present 2 out of 2 patients tested Berrettini % ENG reduced in 87% of patients Grimmer % no testing reported Merchant % no testing reported Zhou % VEMP with increased amplitude and reduced threshold in 88% of patients, absent in 12% of patients VEMP ¼ vestibular evoked myogenic potential testing; ENG ¼ electronystagmonography testing. *In this study, the reported incidence of vestibular symptoms is 10%, but the author goes on to state that vestibular complaints of inconsequential magnitude could be elicited from many patients. proposed that the conductive component of the hearing loss can be explained by a back pressure of perilymphatic and endolymphatic fluid. Theoretically, this results in decreased stapes mobility. As evidence, they site an increased rate of perilymphatic gushers and oozers encountered when the inner ear is opened, either during stapedotomy or cochleostomy. 26,30,67 73 However, this can also be explained by a higher incidence of concurrent cochlear modiolar deficiencies seen in patients with enlarged vestibular aqueducts. Furthermore, acoustic reflexes remain intact, a finding inconsistent with stapes fixation in cases of enlarged vestibular aqueduct. This theory does not explain the high incidence of sensorineural hearing loss as well. In a related line of thinking, Lemmerling 50 theorized that the enlarged vestibular aqueduct allows for greater pressure shifts generated from the intracranial space to cross through the enlarged vestibular aqueduct and damage the inner ear. This could explain why during head trauma or Valsalva hearing loss is seen at a high rate. Okamoto, 74 in a similar argument, proposes that elevated pressures damage the hair cells Electrolyte imbalance theory: Jackler 15 proposed that the endolyphatic sac may be dysfunctional in terms of its physiologic role in inner ear hemostasis. The enlarged and dysfunctional endolyphatic sac results in electrolyte derangement or toxic biproducts that damage the inner ear. He theorized that large volumes of endolymph introduced from the enlarged system might overwhelm the ion pump mechanism of the stria vascularis. As evidence, he sites the Gussen 75 temporal bone study, which demonstrates that the histologic structure of the sac and duct in enlarged vestibular aqueduct cases is clearly abnormal, with thin-walled cyst-like changes in the endolyphatic sac architecture and flattened epithelium along the endolymphatic duct. Other investigators have supported this theory as well. 17,76 3. Hyperosmolar fluid reflux theory: A somewhat similar theory to the electrolyte imbalance theory, Schucknecht 77 along with Levenson 17 and Okamoto 74 theorize that the endolymphatic sac fluid, which is known to contain hyperosmolar fluid, can reflux more easily through the enlarged endolymphatic sac and duct and enter the inner ear resulting in damage to the inner ear structures. Arguing against this theory is an MRI

7 study that found endolymphatic sac volume and intensity vary dynamically and independently of hearing in cases of enlarged vestibular aqueduct. Presumably, intensity of the endolymphatic duct and sac is correlated with hyperosmolarity. However, this study included only two patients! Stapes fixation: Shirazi 76 published an article on a patient who underwent a middle ear exploration for mixed hearing loss and identified the stapes bone as fixed. Attempted stapedotomy was aborted due to a perilymphatic gusher, and postoperative imaging demonstrated an enlarged vestibular aqueduct. 76 This is a single case report. Talbot 79 presents four patients with X-linked congenital mixed hearing loss, enlarged vestibular aqueduct, and fixed stapes footplate. Three of the four underwent stapes surgery with intraoperative findings of a perilymphatic gusher. However, these three patients had other inner ear anomalies, including cochlear base hypoplasia, absent modiolus, and enlarged internal auditory canals. In contrast, Govaerts 26 explored three ears with enlarged vestibular aqueducts and found normal ossicular mobility but absent round window reflexes. Mamikoglu 27 reports exploring a child with enlarged vestibular aqueduct and finding an intact, mobile ossicular chain. Also, Nakashima 36 found that acoustic reflexes persist in cases of enlarged vestibular aqueduct, inconsistent with stapes fixation. 5. Ossicular discontinuity theory: Nakashima 36 suggests air bone gaps seen in some cases are due to ossicular discontinuity based on the results of their study showing the resonant frequency of patients with enlarged vestibular aqueducts was low compared to patients with otosclerosis. They site a temporal bone study demonstrating a 38% incidence of ossicular deformities in enlarged vestibular aqueduct cases Third-window lesion: Third-window lesions are any abnormal opening into the inner ear excluding the normal oval window (first window) and round window (second window). The abnormal opening in the bony labyrinth changes the compliance of the system and results in sound energy being shunted out of the cochlea. Furthermore, the decrease in compliance of the system allows for an enhancement in bone conduction, resulting in the characteristic mixed hearing loss seen in many cases. It can also explain the supranormal bone conduction responses seen in some patients. 81 Vestibular evoked myogenic potential testing in other third-window lesions, such as superior or posterior semicircular canal dehiscence, results in a similar characteristic response as in enlarged vestibular aqueducts, specifically an elevated amplitude of response at a reduced volume of sound. 82 This theory does not, however, explain the deterioration seen in many patients over time. CONCLUSIONS The enlarged vestibular aqueduct remains a common cause of hearing loss in the pediatric population. Although it can be classified as a third window lesion, many questions about its mechanism of action and differences between patients remain a mystery. Little useful prognostic information can be given to families in specific cases, and rehabilitative efforts with hearing aids or cochlear implantation remain the mainstays of treatment. Corticosteroid treatment for sudden hearing loss remains controversial but has little direct evidence demonstrating any benefit. Endolymphatic sac decompression and oblitteration have not been shown to be beneficial and have even been correlated with worsening of symptoms in most investigations. BIBLIOGRAPHY 1. Mondini C. Anatomica surdi nati sectio. De Bononiensi Scientarium et Artium Instituto atque Academia Commenarii. Banoniae 1791:7: Valvassori G, Naunton R, Lindsay J. Inner ear anomalies: clinical and histopathological considerations. Ann Otol Rhinol Laryngol 1989;78: Valvasori G, Clemis J. The large vestibular aqueduct syndrome. Laryngoscope 1978;88: Zalzal G, Sharon T, Vezina L, Bjornsti P, Grundfast K. Enlarged vestibular aqueduct and sensorineural hearing loss in childhood.arch Otolaryngol Head Neck Surg 1995;121: Karet F, Finberg K, Nelson R, et al. Mutations in the gene encoding B1 subunit of HþATPase cause renal tubular acidosis with sensorineural deafness. 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