Computed tomography findings in large vestibular aqueduct syndrome.

CONCLUSIONS: Patients with large vestibular aqueduct syndrome (LVAS) have disturbed morphogenesis of bony labyrinth. Semicircular canal anomalies are common in LVAS. OBJECTIVE: To describe the additional inner ear anomalies on CT imaging in pediatric patients with LVAS, and to investigate the lateral semicircular canal (LSCC) anomalies associated with LVAS by measurement of the LSCC bony island width. PATIENTS AND METHODS: We retrospectively reviewed the digitally stored temporal bone CT imaging obtained for 23 patients with LVAS, additional inner ear anomalies were noted, and measurements of the LSCC bony island width were made on axial CT scans on the workstation. Measurements were compared to the normative data obtained from 20 patients without sensorineural hearing loss. RESULTS: Of the 23 patients (bilateral in 22 and unilateral in 1), additional inner ear malformations were identified in 21 cases presenting either singly or in combination. A small LSCC bony island (<3 mm in diameter) appeared highly typical; vestibule and LSCC anomalies were identified in 13 cases (26 ears) based on visual inspection combined with abnormal measurements. Dehiscence of the superior and/or posterior semicircular canal was identified in 19 ears, and Mondini deformity was identified in 6 ears.

[Large endolymphatic duct and sac syndrome : part 2: clinical manifestations]. / Der erweiterte Ductus und Saccus endolymphaticus : Teil 2: Klinische Manifestationen.

OBJECTIVE: The aim of this study was to clarify the clinical course of large endolymphatic duct and sac syndrome (LEDS). Although LEDS is the most common form of radiologically detectable inner ear malformation associated with sensorineural hearing loss (SNHL), it is relatively unknown in the German-speaking countries. We hoped to derive useful pointers for clinical care. METHODS: We evaluated the clinical audiometric records and imaging findings of 169 patients with clinically suspected inner ear malformation seen between 1994 and 2003. Following identification of all LEDS cases, we serially investigated the anamnestic and functional data with regard to severity and course. RESULTS: Among 169 patients, 17 (median age 12 years; 12 females) showed LEDS. A total of 28 ears were affected. Clinically, most cases were of prelingual or perilingual onset and displayed steady or fluctuatingly progressive severe SNHL with emphasis on the high frequencies or deafness. Episodes of sudden hearing loss were relatively frequent. No correlation could be demonstrated between the severity of morphological changes and the degree of SNHL. CONCLUSION: Progression of SNHL and episodes of sudden hearing loss were seen mainly in late childhood or adolescence. This should be taken into account when informing and advising patients and planning therapy.

[Large endolymphatic duct and sac syndrome (LEDS) : part I: analysis of imaging findings]. / Der erweiterte Ductus und Saccus endolymphaticus : Teil 1: Analyse bildgebender Befunde.

OBJECTIVE: Large endolymphatic duct and sac (LEDS) syndrome is the most common radiologically detectable form of inner ear malformation (IEM) associated with sensorineural hearing loss (SNHL). Nevertheless, it is relatively unknown in the German-speaking countries. METHODS: Among all patients referred from ear, nose, and throat specialists to the radiology department with clinically suspected IEM between 1994 and 2003, we identified the cases of LEDS. The retrospective study included clinical records, high-resolution computed tomography, and magnetic resonance imaging. RESULTS: Of 169 patients, 17 (median age 12 years; 12 females) showed LEDS. A total of 28 ears were affected. Ten patients (6%; 15 ears) had isolated LEDS, while seven patients showed additional IEM (4%; 13 ears). The most frequent of these was dysplastic vestibule (13/13 ears), followed by Mondini deformity (10/13 ears) and dilated semicircular canals (7/13 ears). Three of 13 ears revealed severe IEM of the cochlea, vestibule, and semicircular canals. No correlation could be demonstrated between the severity of morphological changes and the degree of SNHL. CONCLUSION: LEDS may be an underestimated cause of SNHL. Imaging is necessary for a confident diagnosis.

Eya1 regulates the growth of otic epithelium and interacts with Pax2 during the development of all sensory areas in the inner ear.

Members of the Eyes absent (Eya) gene family are important for auditory system development. While mutations in human EYA4 cause late-onset deafness at the DFNA10 locus, mutations in human EYA1 cause branchio-oto-renal (BOR) syndrome. Inactivation of Eya1 in mice causes an early arrest of the inner ear development at the otocyst stage. To better understand the role of Eya1 in inner ear development, we analyzed the cellular and molecular basis of the early defect observed in the Eya1 mutant embryos. We report here that Eya1-/- otic epithelium shows reduced cell proliferation from E8.5 and increased cell apoptosis from E9.0, thus providing insights into the cellular basis of inner ear defect which occurred in the absence of Eya1. Previous studies have suggested that Pax, Eya and Six genes function in a parallel or independent pathway during inner ear development. However, it remains unknown whether Pax genes interact with Eya1 or Six1 during inner ear morphogenesis. To further evaluate whether Pax genes function in the Eya1-Six1 pathway or whether they interact with Eya1 or Six1 during inner ear morphogenesis, we have analyzed the expression pattern of Eya1, Pax2 and Pax8 on adjacent sections of otic epithelium from E8.5 to 9.5 by in situ hybridization and the inner ear gross structures of Pax2, Eya1 and Six1 compound mutants at E17.5 by latex paintfilling. Our data strongly suggest that Pax2 interacts with Eya1 during inner ear morphogenesis, and this interaction is critical for the development of all sensory areas in the inner ear. Furthermore, otic marker analysis in both Eya1-/- and Pax2-/- embryos indicates that Eya1 but not Pax2 regulates the establishment of regional specification of the otic vesicle. Together, these results show that, while Eya1 exerts an early function essential for normal growth and patterning of the otic epithelium, it also functionally synergizes with Pax2 during the morphogenesis of all sensory areas of mammalian inner ear.

The large vestibular aqueduct--case report and review of the literature.

Patients with a large vestibular aqueduct (LVA) suffer from a loss of hearing in childhood at an early onset. An acute loss of hearing can be precipitated by minor head trauma. Until now there seems to be no sufficient therapy for stopping the progression of a loss of hearing. It has been shown that a cochlear implantation is a worthwhile procedure if the patient is almost deaf. We report the case of a patient with a bilateral LVA. A loss of hearing was confirmed at the age of 16 months. Exposure to loud noise triggered an acute progression of the hearing loss. At the age of 18 years, LVA was confirmed radiologically, revealing an enlarged endolymphatic duct and sac in MRI scans and an enlarged vestibular aqueduct in the CT scan. We successfully performed a cochlear implant (MED-EL, Combi 40+ flex). Proceeding from this case report, the paper reviews the literature on LVA.

Can a fixed measure serve as a pertinent diagnostic criterion for large vestibular aqueduct in children?

BACKGROUND: A vestibular aqueduct midpoint width greater than 1.50 mm is currently considered to be pathognomonic for a large vestibular aqueduct syndrome. OBJECTIVE: To analyse the diameter of the vestibular aqueduct in children as a function of age and consequently to determine if a fixed measure could serve as a pertinent diagnostic criterion. MATERIALS AND METHODS: This was a retrospective study of 200 high-resolution CT scans of the ear in 100 patients aged 0-16 years and from various paediatric medical departments. On each CT scan, the lateral semicircular canal diameter, the vestibular aqueduct midpoint width between the external aperture and common crus, and the vestibular aqueduct external aperture diameter were measured. Spearman's rank test and the Mann-Whitney correlation test were used for an integrated statistical analysis. RESULTS: There was no statistically significant variability in vestibular aqueduct diameter as a function of age or sex of patients. CONCLUSION: A CT scan threshold value, fixed and independent of age and sex, is thus legitimate for the diagnosis of vestibular aqueduct dilatation.

Imaging and clinical findings in large endolymphatic duct and sac syndrome.

OBJECTIVE: Large endolymphatic duct and sac syndrome (LEDS) is known as the most common kind of inner ear malformations, which is radiologically detectable. Nevertheless, nowadays many questions are not fully cleared and LEDS is relatively unknown among general radiologists. The aim of this study was to evaluate the incidence of LEDS in the own patient population and to present our experiences regarding imaging findings, clinical presentation and follow up. MATERIALS AND METHODS: Based on a complete recording of all patients, sent from ENT department to radiology, we identified all radiological diagnosed cases of inner ear malformations including LEDS and all patients in whom an inner ear malformation was clinically suspected. The retrospective study included clinical records, HR-CT and MRI performed between 1994 and 2002. RESULTS: Among 169 patients (338 ear), 17 of patients (median age: 12 years) and 28 ears, respectively, had enlarged endolymphatic structures. In 10 patients - 6% - (15 ears), no other abnormalities were detected, called isolated LEDS, seven patients showed additional inner ear abnormalities. One patient showed a labyrinthine hemorrhage after sudden hearing loss. Audiometric data revealed sensorineural hearing loss in 22 ears, deafness in 5 ears and normal hearing in 1 case of 28 ears. In 10 (67%) of 15 ears with isolated LEDS, the hearing loss was downward-fluctuating progressive. Twelve patients (eight with isolated LEDS) had partly repeated sudden hearing losses. A trigger for worsening of hearing was found in five patients. A correlation between the severity of morphological changes on imaging and the degree of hearing disturbances could not be detected. Only four young patients underwent a radiological examination within the first or second year after onset of hearing loss. Three patients received a cochlear implant. CONCLUSIONS: LEDS might be the cause of progressive hearing loss and repeated acute hearing losses in children and young adults. Imaging plays an important role in making the diagnosis.

Enlarged endolymphatic duct and sac syndrome: relationship between MR findings and genotype of mutation in Pendred syndrome gene.

Pendred syndrome (PDS) is characterized by profound deafness in childhood, positive perchlorate challenge, and goiter. PDS is often associated with enlarged endolymphatic duct and sac (EEDS), and recently, PDS gene mutations have been reported even in those patients with EEDS without classic Pendred syndrome. In a previous report, the number of mutant alleles was correlated with the degree of subclinical thyroid abnormality, but not with hearing loss, in patients with missense mutation H723R. It also has been reported that the hearing loss in EEDS was not correlated with the EEDS volume, cochlear modiolar area, or signal intensity of the endolymphatic sac. We evaluated the correlations between the number of mutant alleles and these parameters in patients with EEDS to investigate the mechanisms underlying this condition. The study group was comprised of 16 Japanese patients with EEDS diagnosed by MR imaging. The H723R mutation was homozygous in six patients and heterozygous in six patients, with no mutation found in four patients. The modiolar area, EEDS volume, and signal intensity ratio (sac signal/cerebrospinal fluid signal) were not significantly correlated with the number of mutant alleles. PDS gene mutations may not be the only cause of EEDS, and the mechanisms underlying EEDS remain unclear.

Enlarged vestibular aqueduct in two male siblings.

This report describes the case history of two male siblings with sensorineural hearing loss and an enlarged vestibular aqueduct (EVA). Sibling 1 presented with a history of intermittent self-limiting ataxia and hearing loss at the age of 25 months and sibling 2 presented with a similar history at the age of 18 months. MRI showed an enlarged endolymphatic duct and sac bilaterally in both children. Perchlorate discharge tests were positive in both infants leading to a diagnosis of Pendred syndrome. A number of conditions associated with EVA are discussed with a view to devising management strategies.

MR imaging of the enlarged endolymphatic duct and sac syndrome by use of a 3D fast asymmetric spin-echo sequence: volume and signal-intensity measurement of the endolymphatic duct and sac and area measurement of the cochlear modiolus.

BACKGROUND AND PURPOSE: In enlarged endolymphatic duct (EED) and sac (EES) syndrome, deformity of the EED and EES is congenital; however, hearing loss is acquired. To investigate the pathophysiology of progressive sensorineural hearing loss in EED and EES syndrome, we measured the volume of the EED and EES, the diameter of the EED and EES, the area of the cochlear modiolus, and the signal intensity of the EES and compared our findings against degree of hearing loss. METHODS: Thin-section MR images of 33 ears in 17 patients with EED and EES syndrome were studied. All studies were obtained on a 1.5-T MR unit using a quadrature surface phased-array coil. Heavily T2-weighted 3D fast asymmetric spin-echo images were obtained with a voxel size of 0.3 x 0.3 x 0.8 mm without zero-fill interpolation. Two radiologists traced the areas of the EED and EES manually, and the volume was calculated. The area of the cochlear modiolus, diameter of the EED and EES, and signal intensity of the EES were also measured by drawing regions of interest manually. The signal intensity ratio of EES/CSF was calculated. These measured values were compared against audiographic data, and the degree of linear correlation was determined. RESULTS: The volume of the EED and EES, the area of the modiolus, the diameter of the EED and EES, and the signal intensity of the EES did not show significant correlation with degree of hearing loss. CONCLUSION: These findings suggest that there is a microscopic area of damage or fragility in the inner ear not visible even with thin-section heavily T2-weighted MR imaging.

MR imaging of the cochlear modiolus: area measurement in healthy subjects and in patients with a large endolymphatic duct and sac.

PURPOSE: To evaluate the cochlear modiolus with thin-section magnetic resonance (MR) imaging in healthy subjects and patients with a large endolymphatic duct and sac, and to assess whether the cochlea is normal or abnormal in patients with a large endolymphatic duct and sac. MATERIALS AND METHODS: MR images were obtained in 10 ears in five volunteers (group 1), 40 ears in 20 patients with bilateral sensory hearing loss (group 2), three ears in two patients with Mondini malformation (group 3), and 12 ears in seven patients with a large endolymphatic duct and sac (group 4). RESULTS: In groups 1 and 2, all modiolar areas were larger than 4.0 mm2. In group 3, each modiolus was smaller than 2.0 mm2. In group 4, modiolar areas were smaller than 2.0 mm2 in eight ears and were larger than 4.0 mm2 in four ears. CONCLUSION: Findings in this study confirm that a large endolymphatic duct and sac is frequently associated with modiolar deficiency, but the modiolar area is normal in some cases. This result does not support the recently proposed hypothesis that hearing loss with a large endolymphatic duct and sac is caused by the transmission of subarachnoid pressure forces into the labyrinth through a deficient modiolus.

MR evaluation of vestibulocochlear anomalies associated with large endolymphatic duct and sac.

BACKGROUND AND PURPOSE: Large endolymphatic duct and sac (LEDS) is one of the most common anomalies seen in patients with congenital sensorineural hearing loss (SNHL), and is known to occur with other inner ear findings. Our purpose was to use high-resolution T2-weighted fast spin-echo (FSE) MR imaging to describe the features and prevalence of specific anomalies that occur in association with LEDS. METHODS: We retrospectively reviewed MR images of the inner ear obtained in 63 patients with LEDS and in 60 control subjects. We evaluated each image for features of cochlear and vestibular dysplasia, including deficiency of the cochlear modiolus, gross cochlear dysmorphism, asymmetry of the cochlear scalar chambers, enlargement of the membranous vestibule, gross vestibular dysmorphism, and abnormality of the semicircular canals (SCC). RESULTS: Cochlear anomalies were present in 76% of ears with LEDS. Modiolar deficiency, gross dysmorphism, and scalar asymmetry were seen in 94%, 71%, and 65% of abnormal cochleas, respectively. Vestibular abnormalities were present in 40% of ears with LEDS. Simple enlargement, gross dysmorphism, and distortion of the lateral SCC were seen in 84%, 16%, and 32% of abnormal vestibules, respectively. CONCLUSION: Coexistent cochlear anomalies, vestibular anomalies, or both are present in most ears with LEDS, and appear as a spectrum of lesions, ranging from subtle dymorphism to overt dysplasia. The presence of coexistent anomalies in LEDS affects treatment decisions and prognosis. Newer techniques of high-resolution FSE MR imaging provide a means of exquisite characterization of LEDS, as well as more sensitive detection of associated vestibulocochlear anomalies.

Large endolymphatic duct and sac syndrome--a case report.

A 17-year-old girl with a history of hearing loss, presented with recurrent episodes of vomiting. CT scan revealed bilateral enlarged vestibular aqueducts and MR scanning confirmed the diagnosis of large endolymphatic duct and sac syndrome. This article looks into the anatomy and physiology of the endolymphatic duct and sac as well as possible explanations for the hearing loss associated with this syndrome.

Large vestibular aqueduct syndrome: a genetic disease?

OBJECTIVE: Our objective was to determine the familial incidence of large vestibular aqueduct syndrome (LVAS) detected by CT and MR imaging and to propose the genetic inheritance of LVAS. MATERIALS AND METHODS: We retrospectively reviewed cases of LVAS revealed by temporal-bone CT and MR imaging at the University of Utah Health Sciences Center. We interviewed 25 patients with LVAS regarding family history of hearing loss. Any family members with onset of hearing loss before 30 years old also underwent CT and MR imaging. The vestibular aqueduct (on CT scans) or the endolymphatic duct (on MR images) was measured at the midpoint of the distal limb. A measurement greater than 1.5 mm in diameter was considered abnormally large. Diagnosis of LVAS was made if the patient had hearing loss and positive imaging findings. RESULTS: Of the 25 patients, five were found to have familial involvement, resulting in subsequent study of eight additional symptomatic individuals. A total of 33 patients had positive CT or MR imaging findings. Twenty-nine underwent both studies, two underwent CT only, and two underwent MR imaging only. Among the 33 patients with LVAS, 39% familial occurrence was observed (13 patients). In four of the five different families, the involvement occurred among siblings in one generation. In one of the five families, the involvement occurred in two generations, affecting an uncle and a cousin of the patient. CONCLUSION: In patients with LVAS, a significant subgroup had familial involvement. Based on the pedigrees of the familial cases, the pattern was most consistent with autosomal recessive inheritance, although a smaller component of autosomal dominant or multifactorial inheritance may exist.

Overlapping thin-section fast spin-echo MR of the large vestibular aqueduct syndrome.

PURPOSE: To evaluate a high-resolution, thin-section fast spin-echo MR imaging technique of the inner ear to identify the large vestibular aqueduct syndrome seen on temporal bone CT scans. METHODS: We retrospectively reviewed the temporal bone CT scans of 21 patients with hearing loss and enlarged bony vestibular aqueducts by CT criteria. High-resolution fast spin-echo MR imaging was then performed on these patients using dual 3-inch phased-array receiver coils fixed in a temporomandibular joint holder and centered over the temporal bones. MR imaging included axial and oblique sagittal fast spin-echo sequences. The diameter of the midvestibular aqueduct on CT scans and the signal at the level of the midaqueduct on MR images were measured on axial sequences, then compared. High-resolution MR imaging with the same protocol was performed in 44 control subjects with normal ears, and similar measurements were taken. RESULTS: The average size of the enlarged bony vestibular aqueduct on CT scans was 3.7 mm, and the average width of the signal from within the enlarged aqueduct on MR images was 3.8 mm. Statistical analysis showed excellent correlation. MR images alone displayed the enlarged extraosseous endolymphatic sac, which accompanies the enlarged aqueduct in this syndrome. Five ears in three patients with enlarged bony vestibular aqueducts on CT scans showed no evidence of an enlarged endolymphatic duct or sac on MR images. An enlarged endolymphatic sac was seen on MR images in one patient with a bony vestibular aqueduct, which had normal measurements on CT scans. MR imaging alone identified a single case of mild cochlear dysplasia (Mondini malformation). In the 88 normal ears studied, the average size of the endolymphatic sac at its midpoint between the common crus and the external aperture measured on MR images was 0.8 mm (range, 0.5 to 1.4 mm). In 25% of the normal ears, no signal was seen from within the vestibular aqueduct. CONCLUSION: Thin-section, high-resolution fast spin-echo MR imaging of the inner ear is complementary to CT in studying patients with the large vestibular aqueduct syndrome, as MR imaging better displays the soft tissue and fluid of the membranous labyrinth.

Inner ear malformations in patients with sensorineural hearing loss: detection with gradient-echo (3DFT-CISS) MRI.

The sensitivity of different MRI sequences in the detection of inner ear malformations in patients presenting with sensorineural hearing loss (SNHL) and/or vertigo was evaluated. We studied 650 patients presenting with SNHL and/or vertigo, clinically not suspected of having inner ear malformations. The sensitivity of T1-weighted, Gd-enhanced T1-weighted and (when available) T2-weighted spin-echo images, and three-dimensional Fourier transformation-constructive interference in steady state (3DFT-CISS) gradient-echo images, to unexpected malformations was assessed. Inner ear malformations were found in 15 (2.3%) of these patients. Enlargement of the endolymphatic duct and sac was the most frequent malformation, found in 11 patients. The 3DFT-CISS images showed all lesions; the other sequences were less sensitive and the pathology was missed, partially or only retrospectively seen in 11 of the 15 patients. Therefore, in addition to the routine unenhanced and Gd-enhanced T1-weighted and T2-weighted images, thin gradient-echo (3DFT-CISS) images are necessary to detect all clinically unexpected inner ear malformations in patients presenting with vertigo and/or SNHL.

Advanced techniques in magnetic resonance imaging in the evaluation of the large endolymphatic duct and sac syndrome.

The purpose of this report is to compare temporal bone computed tomography (CT) to high-resolution magnetic resonance (MR) imaging using a novel thin-section fast spin echo (FSE) pulse sequence in identifying and characterizing patients with large vestibular aqueduct syndrome. Sixteen patients with sensorineural hearing loss and a CT diagnosis of large vestibular aqueduct(s) underwent high-resolution fast spin echo magnetic resonance imaging with dual, 3-in phased array receiver coils centered over the external auditory canals. Magnetic resonance imaging parameters included axial and oblique sagittal fast spin echo with an effective slice thickness of 1 mm contiguous. Thirty-eight patients with 76 normal inner ears who underwent MR imaging using this technique had their endolymphatic duct measured. MR alone identified the enlarged endolymphatic sac seen along with the large endolymphatic duct in all cases. Three cases (five inner ears) with enlarged bony vestibular aqueducts on CT showed no evidence of endolymphatic duct or sac enlargement on MR. MR alone identified a single case of mild cochlear anomaly in conjunction with an enlarged endolymphatic duct and sac. In the normal population the size of the normal endolymphatic duct at its midpoint measured from 0.1 to 1.4 mm. Thin-section, high-resolution fast spin echo MR imaging of the inner ear may be superior to CT in the evaluation of patients with the large vestibular aqueduct syndrome.