Search

BackgroundMénière's disease (MD) is a chronic inner ear disorder with a multifactorial etiology. Decreased visualization of the endolymphatic duct (ED) and sac (ES) is thought to be associated with MD, although controversy exists about whether this finding is specific to MD. Recent literature has revealed that two distinct ES pathologies, developmental hypoplasia and epithelial degeneration, can be distinguished in MD using the angular trajectory of the vestibular aqueduct (ATVA) or ED-ES system as a radiographic surrogate marker. It has been suggested that these two subtypes are associated with distinct phenotypical features. However, the clinical differences between the ATVA subtypes require further validation.Research objectiveThe objective of this study is to investigate whether (1) non-visualization of the ED-ES system is a discriminative radiological feature for MD in a cohort of vertigo-associated pathologies (VAPs) and whether (2) different angular trajectories of the ED-ES system in MD are associated with distinguishable clinical features.SettingThe study was conducted in the Vertigo Referral Center (Haga Teaching Hospital, The Hague, the Netherlands).MethodsWe retrospectively assessed 301 patients (187 definite MD and 114 other VAPs) that underwent 4h-delayed 3D FLAIR MRI. We evaluated (1) the visibility of the ED-ES system between MD and other VAP patients and (2) measured the angular trajectory of the ED-ES system. MD patients were stratified based on the angular measurements into αexit ≤ 120° (MD-120), αexit 120°-140° (MD-intermediate), or αexit ≥ 140° (MD-140). Correlations between ATVA subgroups and clinical parameters were evaluated.ResultsNon-visualization of the ED-ES system was more common in definite MD patients compared with other VAPs (P < 0.001). Among definite MD patients, the MD-140 subtype demonstrated a longer history of vertigo (P = 0.006), a higher prevalence of bilateral clinical disease (P = 0.005), and a trend toward a male preponderance (p = 0.053). No significant differences were found between ATVA subgroups regarding the presence or severity of auditory symptoms, or the frequency of vertigo attacks.ConclusionNon-visualization of the ED-ES system is significantly associated with MD. Among MD patients with a visible ED-ES system, we demonstrated that the MD-140 subtype is associated with a longer disease duration, a higher prevalence of bilateral MD, and a trend toward a male preponderance.

We describe progressive multifocal leukoencephalopathy (PML) as an extremely rare cause of unilateral sensorineural hearing loss. A 46-year-old HIV-infected and immunocompromised patient suffered from hearing loss in the left ear since several days. Because of the discrepancy between the normal tone audiogram and the abnormal speech audiogram, MRI was indicated. The scan showed a hyperintense lesion at the left side of the cerebellum, extending to the cranial portion of the medulla oblongata. The lesion was initially diagnosed as PML. Since the symptoms progressed despite earlier initiated and effective treatment with combination antiretroviral therapy, the disease was eventually interpreted as PML-immune reconstruction inflammatory syndrome (PML-IRIS). This case demonstrates that the diagnosis of PML or PML-IRIS should be considered as cause of hearing loss in immunocompromised patients. Also, the importance of complete audiological evaluation including speech audiometry in analysis of subjective hearing impairment is illustrated.

Research Objective: To investigate the correlation between clinical features and MRI-confirmed endolymphatic hydrops (EH) and blood-labyrinth barrier (BLB) impairment.Study Design: Retrospective cross-sectional study.Setting: Vertigo referral center (Haga Teaching Hospital, The Hague, the Netherlands).Methods: We retrospectively analyzed all patients that underwent 4 h-delayed Gd-enhanced 3D FLAIR MRI at our institution from February 2017 to March 2019. Perilymphatic enhancement and the degree of cochlear and vestibular hydrops were assessed. The signal intensity ratio (SIR) was calculated by region of interest analysis. Correlations between MRI findings and clinical features were evaluated.Results: Two hundred and fifteen patients with MRI-proven endolymphatic hydrops (EH) were included (179 unilateral, 36 bilateral) with a mean age of 55.9 yrs and median disease duration of 4.3 yrs. Hydrops grade is significantly correlated with disease duration (P < 0.001), the severity of low- and high-frequency hearing loss (both P < 0.001), and the incidence of drop attacks (P = 0.001). Visually increased perilymphatic enhancement was present in 157 (87.7%) subjects with unilateral EH. SIR increases in correlation with hydrops grade (P < 0.001), but is not significantly correlated with the low or high Fletcher index (P = 0.344 and P = 0.178 respectively). No significant differences were found between the degree of EH or BLB impairment and vertigo, tinnitus or aural fullness.Conclusion: The degree of EH positively correlates with disease duration, hearing loss and the incidence of drop attacks. The BLB is impaired in association with EH grade, but without clear contribution to the severity of audiovestibular symptoms.

Numerous studies have shown the recovery of auditory function in mouse models of genetic hearing loss following AAV gene therapy, yet translation to the clinic has not yet been demonstrated. One limitation has been the lack of human inner ear cell lines or tissues for validating viral gene therapies. Cultured human inner ear tissue could help confirm viral tropism and efficacy for driving exogenous gene expression in targeted cell types, establish promoter efficacy and perhaps selectivity for targeted cells, confirm the expression of therapeutic constructs and the subcellular localization of therapeutic proteins, and address the potential cellular toxicity of vectors or exogenous constructs. To begin to address these questions, we developed an explant culture method using native human inner ear tissue excised at either fetal or adult stages. Inner ear sensory epithelia were cultured for four days and exposed to vectors encoding enhanced green fluorescent protein (eGFP). We focused on the synthetic AAV9-PHP.B capsid, which has been demonstrated to be efficient for driving eGFP expression in the sensory hair cells of mouse and non-human primate inner ears. We report that AAV9-PHP.B also drives eGFP expression in fetal cochlear hair cells and in fetal and adult vestibular hair cells in explants of human inner ear sensory epithelia, which suggests that both the experimental paradigm and the viral capsid may be valuable for translation to clinical application.