Pathogenesis and Etiology of Ménière Disease

Rizk, Habib G.; Mehta, Neil; Qureshi, Uneeb; Yuen, Erick; Zhang, Kathy; Nkrumah, Yaw; Lambert, Paul R.; Liu, Yuan F.; McRackan, Theodore R.; Meyer, Ted A.

doi:10.1001/jamaoto.2021.4282

Cited by 39 publications

(22 citation statements)

References 123 publications

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“…Thus, NF-κB may negatively regulates SGK1, leading to MD pathogenesis through positive regulatory loops with NLRP3 and IL-1β. In addition to immune factors, viral infections and autoimmune or structural dysfunction of the inner ear have been reported as causes of MD 60 . IL-1β expression levels are elevated during bacterial or fungal infections 61 – 63 , or inflammation in patients with active autoimmune diseases 64 , 65 .…”

Section: Discussionmentioning

confidence: 99%

Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model

Zhang

Liu

et al. 2023

Nat Commun

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Ménière’s disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière’s disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière’s disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1β production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk−/− mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière’s disease pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model

Zhang

Liu

et al. 2023

Nat Commun

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“…In the last few years, the scientific interest in the etiology, pathogenesis, radiology, and histopathology of MD has resulted in a great number of publications (for a review, see Refs. (9)(10)(11)(12)(13)). Supplemental Table 5, http://links.lww.…”

Section: Discussionmentioning

confidence: 99%

Differential Volume Increase of Endolymphatic Compartments in Ménière's Disease Is Inversely Associated With Membrane Thickness

2023

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Objectives Our aim in this study was to characterize the morphology of the endolymphatic compartment on histopathology in individuals with Ménière's disease (MD) and to determine why hydrops of the saccule is more pronounced than that of other compartments of the inner ear in MD. Methods Temporal bones from 9 patients with idiopathic MD and from 10 individuals without MD/endolymphatic hydrops were examined. The inner ear fluid compartments in normal ears, and ears with MD were three-dimensionally reconstructed and their volume was calculated. The thickness of the membranes of the labyrinth was measured, and both ruptures of the membranes and patency of the utriculoendolymphatic (UEV; Bast's) valve were assessed. Results In ears with MD, the saccule and the cochlear duct were most frequently hydropic; the utricle was involved approximately half as frequently. In ears without MD, the Reissner's membrane and the membranous wall of the saccule were thinner than that of the utricle and of the lateral semicircular canal (p < 0.01). The lateral semicircular canal did not show signs of hydrops. In all ears with MD in which the utricle exceeded the average volume of normals (6 of 12), the UEV was open or there was a rupture in the utricle. Conclusion Increases in endolymphatic pressure may cause a primary swelling of the apical cochlear duct and saccule, both of which have relatively thin membranes. Hydrops in the utricle may occur less frequently because of a thicker wall, because of a functioning UEV, and when the saccule has already occupied most of the vestibular perilymphatic space.

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“…Pathophysiologie und Ätiologie des Morbus Menière sind trotz vieler Untersuchungen nicht sicher geklärt 21 . Der pathognomische histopathologische Befund ist ein Endolymphhydrops (EH), der aber nicht spezifisch ist und sich auch bei anderen Innenohrerkrankungen findet 22 .…”

Section: Leitsymptom: Rezidivierende Schwindelepisodenunclassified

Die sechs häufigsten peripherenvestibulären Syndrome

Strupp¹,

Zwergal²,

Goldschagg³

2023

Nervenheilkunde

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ZUSAMMENFASSUNGPeriphere vestibuläre Syndrome beruhen auf einer Funktionsstörung des Labyrinths und/oder des Nervus vestibulocochlearis. Phänomenologisch und pathophysiologisch lassen sich 3 Formen klinisch unterscheiden: 1. Rezidivierende Schwindelepisoden mit je nach Ursache unterschiedlicher Dauer, unterschiedlichen Begleitsymptomen und Auslösern. Die zugrunde liegenden Erkrankungen sind der Benigne periphere paroxysmale Lagerungsschwindel, Morbus Menière, Vestibularisparoxysmie und das Syndrom der dritten mobilen Fenster. 2. Das akute vestibuläre Syndrom, bedingt durch eine akute vestibuläre Tonusdifferenz mit dem Leitsymptom heftiger langdauernder Drehschwindel: die akute unilaterale Vestibulopathie/Neuritis vestibularis. 3. Persistierender Schwankschwindel und Gangunsicherheit bedingt durch ein bilaterales vestibuläres Defizit: die bilaterale Vestibulopathie. Für alle diese Erkrankungen liegen Diagnosekriterien der Bárány-Society vor, die gleichermaßen wichtig sind für die klinische Praxis und für wissenschaftliche Studien. Für die Behandlung peripherer vestibulärer Syndrome werden in Abhängigkeit von der Ursache 5 Therapieprinzipien eingesetzt: 1. Sorgfältige Aufklärung des Patienten über Art und Ursache der Beschwerden und die Therapieeffekte; dies ist auch wichtig für die Compliance des Patienten. 2. Physikalisch-medizinische Behandlung: A) Bogengangspezifische Befreiungsmanöver: für den posterioren Kanal das SémontPlus-Manöver, das dem Sémont- und Epley- Manöver überlegen ist; für den horizontalen Kanal das modifizierte Roll-Manöver und für den anterioren Bogengang das modifizierte Yacovino-Manöver. B) Balancetraining bei sensorischen Defiziten (hohe Evidenz). 3. Symptomatische oder kausale medikamentöse Behandlung. Hier mangelt es weiterhin an placebokontrollierten Pharmakotherapiestudien, sodass die Evidenzlage niedrig ist und ein hoher klinischer Forschungsbedarf besteht. 4. Operative Maßnahmen, z. B. bei dem Syndrom der dritten mobilen Fenster. 5. Bei funktionellem Schwindel psychotherapeutische Verfahren.

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Pathogenesis and Etiology of Ménière Disease

Cited by 39 publications

References 123 publications

Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model

Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model

Differential Volume Increase of Endolymphatic Compartments in Ménière's Disease Is Inversely Associated With Membrane Thickness

Die sechs häufigsten peripherenvestibulären Syndrome

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