The enlarged vestibular aqueduct syndrome (EVAS) is a clinical disease causing anatomical abnormality of bony canal in the temporal bone containing endolymphatic duct and sac. It is also associated with progressive sensorineural hearing loss with an isolated enlarged vestibular aqueduct. Familial inheritance of enlarged vestibular aqueduct syndrome (FEVAS) is rare and the correct mode of inheritance is not yet discovered. We studied familial inheritance in EVAS by performing clinical, audiological, radiographic and chromosomal analyses, and found strong indications that FEVAS may be an autosomal recessive trait. Further study would be focused on genetic evaluation of FEVAS.
Endolymphatic Duct ; Extravehicular Activity ; Hearing Loss, Sensorineural ; Temporal Bone ; Vestibular Aqueduct* ; Wills

Enlarged vestibular aqueduct syndrome (EVAS) is well known congenital bony ear anomaly. It's audiologic symptoms and radiological findings are reported in many literatures. However vestibular symptoms of EVAS are rarely reported. A patient with right EVAS developed sudden spinning vertigo on casual observation. He is diagnosed as bilateral benign paroxysmal positional vertigo and recovered by canal repositioning maneuver. We present this case with reviews of previous literatures.
Dizziness ; Ear ; Extravehicular Activity ; Hearing Loss, Sensorineural ; Humans ; Vertigo ; Vestibular Aqueduct

A myriad of the retrospective studies have shown the benefit of hormone replacement therapy (HRT) on cardiovascular disease. It has been consistently shown that estrogen decreases total and LDL cholesterol, but increases the HDL cholesterol, resulting in a favorable cardiovascular outcome. In addition, it has been reported that estrogen has a beneficial role toward vascular function. The benefit of HRT on cardiovascular disease did not become a matter for suspicion or skepticism until the arrival of primary and secondary prevention clinical trial data. A large body of evidence from secondary prevention trials, such as HERS, EVA and WAVE, revealed that HRT has no beneficial effect at all toward cardiovascular disease protection; conversely, it was revealed to even be harmful. HRT increased the risk of CHD, DVT and strokes, as well as of cancers in postmenopausal women with CHD, with the worst evidence coming from a primary prevention trial. The Women's Health Initiative (WHI) study, the largest of the HRT trials, revealed the same findings as those of secondary prevention trials. In this trial, HRT significantly increased the risks of CHD, DVT, strokes and cancers, further confirming the previous findings. The lack of benefit of HRT in those trials can not be explained by the beneficial influence of HRT on the lipid profile and vascular function. Many researchers that still regard HRT as cardioprotective argue that the route, combination of drugs or even the dose of the drug administered would make differences. However, it is the increased VLDL synthesis and risk of thrombosis that make HRT harmful. HRT increase, VLDL synthesis that results in the generation of atherogenic small dense LDL and thrombus formation. In addition, HRT increases the risk of thrombosis by activating the coagulation pathway independently of VLDL synthesis. It has been reported that transdermal estrogen therapy does not increase VLDL synthesis or thrombus formation, being allegedly beneficial. However, it should not be forgotten that even the present data is not decisive and not confirmative for performing another new clinical trial of HRT being potentially harmful
Cardiovascular Diseases* ; Cholesterol, HDL ; Cholesterol, LDL ; Cholesterol, VLDL ; Estrogens ; Extravehicular Activity ; Female ; Hormone Replacement Therapy* ; Humans ; Primary Prevention ; Retrospective Studies ; Secondary Prevention ; Stroke ; Thrombosis ; Women's Health

BACKGROUND AND OBJECTIVES: Unilateral vestibular loss can be induced by intratympanic gentamicin instillation. Despite accumulated reports on the morphologic changes after gentamicin treatment, there are limited reports regarding the effects of gentamicin ototoxicity on the vestibulo-ocular reflex (VOR), in especially unilateral vestibular deficit by local gentamicin instillation. Aim of this study is to provide the functional changes after local gentamicin application in guinea pigs. MATERIALS AND METHODS: Ten white guinea pigs (5 each for control and gentamicin treatment group) were used. Following surgical exposure of the left bulla, 0.9% saline solution or 40 mg/ml of gentamicin soaking gelfoam were applied on the round window. Horizontal vestibulo-ocular reflex (hVOR) was tested during earth vertical axis (EVA) sinusoidal harmonic acceleration rotation at 4 frequencies (0.04, 0.08, 0.16 and 0.32 Hz, 60 deg/sec of peak velocity). In one gentamicin treated animal, hVOR was tested during step velocity off-vertical axis rotation (OVAR) to clockwise and counterclockwise direction (30 degrees forward tilt from EVA with constant velocity of 100 deg/sec). Every test was repeated before treatment and at 2 days, 5 days and 7 days after treatment. RESULTS: The hVOR gain was significantly lowered after gentamicin treatment at all tested frequencies (p<0.05), while the gain does not change over time in control animals. Loss of bias component was evident and some decrease of modulation component was observed in counter-clockwise (lesion side) rotation after gentamicin treatment. CONCLUSION: This study provides characteristics of hVOR during EVA rotation and OVAR in unilateral vestibular deficit animal model by intrabullar gentamicin application.
Acceleration ; Animals ; Axis, Cervical Vertebra ; Bias (Epidemiology) ; Blister ; Extravehicular Activity ; Gelatin Sponge, Absorbable ; Gentamicins ; Guinea ; Guinea Pigs ; Humans ; Models, Animal ; Reflex, Vestibulo-Ocular ; Sodium Chloride

OBJECTIVES: To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. METHODS: Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted. RESULTS: The results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function. CONCLUSION: In summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness.
Asian Continental Ancestry Group ; Child ; Clinical Coding ; Computer Simulation ; Deafness ; Exons ; Extravehicular Activity ; Frameshift Mutation ; Hearing Loss ; Heterozygote ; Humans ; Introns ; Mass Screening ; Parents ; Sequence Homology ; Siblings ; Vestibular Aqueduct

BACKGROUND AND OBJECTIVES: Mutations of the SLC26A4 gene cause congenital hearing loss and enlarged vestibular aqueduct (EVA). A considerable proportion of patients with SLC26A4 mutations have significant residual hearing at birth that eventually worsen and become the cause for cochlear implantation (CI) later in their adolescence or adulthood. We analyzed the auditory outcome and prognostic factors of CI in patients with EVA and biallelic SLC26A4 mutations showing progressive early-onset hearing loss, who eventually had implantation in their adolescent or adult periods. SUBJECTS AND METHOD: Sixteen patients with EVA carrying biallelic SLC26A4 mutations who received CI after 12 years of age were included for analysis. The outcome and prognostic factors of CI were analyzed. The postoperative follow-up period ranged from 3 to 48 months. RESULTS: The age at CI ranged from 12 to 44 years. The categories of auditory performance score was significantly improved after CI from 3.1 to 4.9 (p < 0.05). The mean sentence scores improved significantly in the auditory-visual and auditory-only conditions (p < 0.05). The significant prognostic factors were measurable bone conduction thresholds, preoperative residual hearing, recent history of sudden aggravation of hearing loss, and preoperative speech intelligibility rating scores. There was a tendency of lower postoperative sentence scores in the group with homozygous H723R mutation, but statistical significance was not reached. CONCLUSION: Despite the early-onset of hearing loss, significant improvement in auditory performance can be expected after CI in adolescent and adult patients with EVA and biallelic SLC26A4 mutations. Significant prognostic factors should be considered in selecting candidates and preoperative counseling for CI.
Adolescent* ; Adult* ; Bone Conduction ; Cochlear Implantation* ; Cochlear Implants* ; Counseling ; Extravehicular Activity ; Follow-Up Studies ; Hearing ; Hearing Loss ; Humans ; Methods ; Parturition ; Speech Intelligibility ; Vestibular Aqueduct*