The Overall goal of the proposed project is to describe the effects of Meniere's disease on the individual endorgans and vestibular ganglion, and how the pathology relates to the clinical history and vestibular function on routine testing. We propose a prospective study of the vestibular periphery in Meniere's disease using specimens obtained from ablative inner ear surgery and postmortem specimens. The project will use 1) histopathologic analysis, immunohistochemistry, and electron microscopy to study vestibular pathology 2) unbiased stereology to obtain morphometric measures at multiple levels: neuroepithelium, the nerve fibers, and Scarpa's ganglion neurons in the same subject 3) clinico-pathological correlations and comparisons between morphometric parameters and standarized vestibular testing. Morphometric parameters to be studied include 1) regional total type I, type II, and supporting cell counts in each of the five vestibular endorgans 2) vestibular nerve fiber counts and diameter distribution 3) Scarpa's ganglion neuronal counts and volume distribution. Archival temporal bones from patients with Meniere's disease will be used for Scarpa's ganglion neuronal counts. Using this systematic, prospective design we hope to answer important clinical questions such as 1) Does Meniere's disease affect the individual endorgans differently? 2) Can the patterns of neuroepithelial endorgan damage be correlated with clinical history? 3) Does Meniere's disease affect the vestibular nerve and ganglion? 4) Is Meniere's disease associated with an atrophy of the Scarpa's ganglion neurons? 5) Are clinical phenomenon such as Tumarkin falls, delayed endolymphatic hydrops, and chronic dysequilibrium associated with particular patterns of neuroepithelial or differential endorgan damage? or with alterations in neuronal number or size? 6) What are the morphometric correlates to abnormalities on traditional vestibular testing: caloric paresis, and decreased gain and time constant on step rotational testing?

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-6 (01))
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Miller, Roger
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Calzada, Audrey P; Balaker, Ashley E; Ishiyama, Gail et al. (2012) Temporal bone histopathology and immunoglobulin deposition in Sjogren's syndrome. Otol Neurotol 33:258-66
Calzada, Audrey P; Lopez, Ivan A; Ishiyama, Gail et al. (2012) Otolithic membrane damage in patients with endolymphatic hydrops and drop attacks. Otol Neurotol 33:1593-8
Duong, Trac; Lopez, Ivan A; Ishiyama, Akira et al. (2011) Immunocytochemical distribution of WARP (von Willebrand A domain-related protein) in the inner ear. Brain Res 1367:50-61
Ishiyama, Gail; Geiger, Christopher; Lopez, Ivan A et al. (2011) Spiral and vestibular ganglion estimates in archival temporal bones obtained by design based stereology and Abercrombie methods. J Neurosci Methods 196:76-80
Miller, Mia E; Makary, Chadi; Lopez, Ivan A et al. (2010) Endolymphatic hydrops in otologic syphilis: a temporal bone study. Otol Neurotol 31:681-6
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Ishiyama, Akira; Mowry, Sarah E; Lopez, Ivan A et al. (2009) Immunohistochemical distribution of basement membrane proteins in the human inner ear from older subjects. Hear Res 254:1-14
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Ishiyama, Gail; Lopez, Ivan; Baloh, Robert W et al. (2007) Histopathology of the vestibular end organs after intratympanic gentamicin failure for Meniere's disease. Acta Otolaryngol 127:34-40
Lopez, Ivan; Ishiyama, Gail; Tang, Yong et al. (2005) Regional estimates of hair cells and supporting cells in the human crista ampullaris. J Neurosci Res 82:421-31