Contemporary perspectives on the pathophysiology of Meniere's disease: implications for treatment

Meniere's disease is characterized by episodic vertigo, fluctuating hearing loss, aural fullness and tinnitus. Endolymphatic hydrops, found on post-mortem examination, is the histologic hallmark. Recent research suggests that endolymphatic hydrops results from cytochemical perturbations of unknown etiology that lead to disturbance of the normal endolymphatic fluid homeostasis. This consequent hydropic state or the associated cytochemical perturbations appears to create a neurotoxic environment that ultimately leads to spiral ganglion cell death likely via the apoptotic mechanism. This review highlights some of the recent advances in the understanding of the pathophysiology of endolymphatic hydrops and progressive cochleovestibular deterioration, with emphasis placed on its potential therapeutic implications. Recent evidence supports that endolymphatic hydrops is possibly an epiphenomenon, and is preceded by perturbation of the normal ionic transport regulatory mechanisms. Furthermore, chronic cochleovestibular deterioration appears to be the result of an excitotoxic response to chronic hydrops. A recently described animal model, the Phex mouse, carrying a mutation in the Phex Hyp-Duk gene, provides a novel insight to genetically regulated postnatal endolymphatic hydrops and a useful tool to expand our understanding. Despite encouraging recent advances, there are considerable challenges that remain in the development of targeted therapeutic interventions that may offer new avenues of neuroprotection in known cases of Meniere's disease. These advances will hopefully provide pharmacotherapeutic interventions aimed at preventing progressive cochleovestibular dysfunction.