http://www.sciencedirect.com/science/article/pii/S1568997212000092 Meniere's disease might be an autoimmune condition? A. Greco, A. Gallo, M. Fusconi, C. Marinelli, G.F. Macri, , M. de Vincentiis Show more doi:10.1016/j.autrev.2012.01.004Get rights and content Under a Creative Commons license Open Access Abstract Objectives To review our current knowledge of the pathogenesis of Meniere's disease, including viral infection and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy. Systematic review methodology Relevant publications on the aetiopathogenesis, molecular biology, genetics and histopathology of Meniere's disease from 1861 to 2011 were analysed. Results and conclusions Meniere's disease is characterised by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The aetiology and pathogenesis remain unknown. Proposed theories of causation include viral infections and immune system-mediated mechanisms. The immune response in Meniere's disease is focused on inner ear antigens. Approximately one-third of Meniere's disease cases seem to be of an autoimmune origin although the immunological mechanisms involved are not clear. The diagnosis of autoimmune inner ear disease is based either on clinical criteria or on a positive response to steroids. The antiviral approach has virtually eliminated the use of various surgical methods used in the past. Steroid responsiveness is high, and with prompt treatment, inner ear damage may be reversible. The administration of etanercept improves or stabilises symptoms in treated patients. Treatment of antiphospholipid syndrome can be directed toward preventing thromboembolic events by using antithrombotic medications. Only warfarin has been shown to be effective. Gene therapy can be used to transfer genetic material into inner ear cells using viral vectors and to protect, rescue, and even regenerate hair cells of the inner ear. Keywords Meniere's disease; Histopathology; Aetiopathogenesis; Therapy 1. Introduction Prosper Meniere first described Meniere's disease in 1861 [1]. He challenged the general terminology at the time that called this disease apoplectic cerebral congestion, implying a disorder of the brain. Meniere described this pathology as being associated with the peripheral end organ of the inner ear rather than the brain. He and other investigators called it “glaucoma of the ear” [2] and [3]. In 1927, Guild [4] identified the endolymphatic sac as the site of the “outflow of endolymph”. Later that same year, Portmann [3] described his first endolymphatic sac surgery for Meniere's disease. The following year, in 1928, Dandy [5] proceeded with vestibular neurectomy, which attempted to isolate the vestibular system from the brain and thus cure patients of vertigo. In 1943, Altmann and Fowler [6] concluded that problems in production and absorption of endolymph can lead to Meniere's disease. In a landmark study in 1967, Kimura [7] developed the first animal model using guinea pigs and showed that blockage of the endolymphatic sac and duct causes obstruction of endolymphatic outflow, leading to hydrops of the inner ear. Meniere's disease remains a difficult disease to diagnose, especially in the early stages when not all of the symptoms may be present. Few articles have been published on the epidemiology of Meniere's disease. In 1973, Stahle and colleagues reported a prevalence of 46 cases per 100,000 people [8]. From 1975, several studies indicated a prevalence of 17 cases per 100,000 people [9] and [10]. Kotimaki and colleagues reported a prevalence of 43 per 100,000 and an average yearly incidence of 4–3 per 100,000 people in the population [11]. Most studies suggest a female preponderance of up to 1–3 times that in men. The disease seems to be much more common in adults in their fourth and fifth decades than in younger people, although it has been reported to occur in children [12]. A strong positive family history exists in patients with Meniere's disease. Several studies have indicated that up to 20% of family members have similar symptoms [13] and [14]. Meniere's disease is characterised by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure [15]. It has been classified into typical Meniere's disease, with all the before mentioned cochlear and vestibular symptoms, and atypical Meniere's disease, with either cochlear symptoms (e.g. hearing loss, tinnitus and aural pressure) or vestibular symptoms (e.g. vertigo with aural pressure) [16]. 1.1. Pathophysiology The primary histopathological correlate of Meniere's disease is endolymphatic hydrops. Paparella used the notion of a “lake, river, and pond” to explain the occurrence of malabsorption of endolymph leading to hydrops [15]. This notion describes the endolymphatic sac as a pond, the vestibular aqueduct as a river, and the endolymphatic fluid space as a lake. When there is an obstruction near the endolymphatic sac or duct, a backlog of endolymphatic fluid is created, leading to hydrops. The first temporal bone histopathological studies of Meniere's disease by Hallpike, Cairns [16] and [17] and Yamakawa [18] reported a ballooning distension of the endolymphatic system, a finding that is almost invariably seen in documented Meniere's disease [19] and [20]. Previous temporal bone studies demonstrated evidence for endolymphatic membrane rupture or fibrosis around the endolymphatic sac; however, further temporal bone studies did not provide evidence for fibrosis of the endolymphatic sac [21]. Vestibular fibrosis between the saccular wall and the stapes footplate has been observed in 35% of human temporal bones extracted from Meniere's disease patients (Picture 1) [20], [21] and [22]. A recent human temporal bone study [19] suggested that the endolymphatic hydrops in Meniere's disease is “a marker for a disordered homeostasis of the labyrinth in which some factor (as yet unknown) produces both the clinical symptoms of Meniere's syndrome and endolymphatic hydrops”. Full-size image (23 K) Picture 1. Horizontal section through the vestibule of patient demonstrates fibrous tissue (*) surrounding a dilated saccular wall (arrow heads) under the stapes footplate (F). S = Saccular macula (Gacek RR. Meniere's disease is a viral neuropathy. ORL 2009; 71: 78–86.). Figure options Furthermore, primary and secondary endolymphatic hydrops have been documented in the temporal bones of subjects without symptoms of Meniere's disease [19]; thus, hydrops is likely an epiphenomenon. Previous histopathological studies of surgically obtained endorgans from Meniere's disease patients at the light microscopic level have posited a relative preservation of the vestibular neuroepithelium [20], [23] and [24]. In many prior studies, though, only the utricular macula was systematically evaluated. More recently, it was found that the majority of the vestibular endorgans demonstrated variable degrees of neuroepithelial degeneration, including conversion of the sensory epithelium to a monolayer, basement membrane thickening, cellular vacuolisation, absence of hair cell stereocilia, and increased intercellular stromal space. The utricular macula was relatively spared (Picture 2) [25]. Full-size image (75 K) Picture 2. Sensory epithelia from Meniere's disease vestibular endorgans. (Mc Call AA, Ishiyama GP, Lopez IA, Bhuta S, Vetter S, Ishiyama A. Histopathological and ultrastructural analysis of vestibular endorgans in Meniere's disease reveals basement membrane pathology. BMC Ear Nose Throat Disorders 2009; 3; 9: 4.). Figure options The pathogenesis of Meniere's disease is still unknown; however, it has been proposed that viral infections and autoimmune processes may play a role in the induction of the disease. 1.2. Viral hypothesis Endolymphatic hydrops of the membranous labyrinth has been recognised as the pathological correlate of Meniere's disease for over 70 years [17] and [18]. Obstruction of endolymph flow has been implicated as the cause of endolymphatic hydrops [26] and [27]. Significant questions to this proposed pathophysiological mechanism persist. First, although endolymphatic hydrops is readily produced by surgical obliteration of the endolymphatic sac in lower organisms (guinea pig, chinchilla, gerbil), it does not occur in higher mammals (cat, monkey) [28]. Second, imbalance (vertigo) has not been observed in these animal models. Third, the temporal bones of animal models with experimentally induced endolymphatic hydrops do not contain fibrous tissue adjacent to the stapes footplate with attachment to the saccular wall. Viral infection has been advocated as a possible cause of Meniere's disease by many authors [29] and [30]. It has also been postulated that certain viruses have more affinity than others for affecting the inner ear [31]. For this reason, many studies have been carried out to verify whether viruses such as the neurotropic viruses, herpes simplex virus (HSV) types 1 and 2 [32], varicella zoster virus (VZV), and cytomegalovirus (CMV) [33], can cause Meniere's disease by invading the endolymphatic sac. The endolymphatic sac is known to be the site of immune reaction due to the existence of lymphocytes and immunoglobulins in addition to the resorption of endolymphatic fluid [34] and [35]. Traditionally, to prove that a clinical syndrome is caused by an organism, Koch's postulates must be satisfied. While such an approach is possible for bacterial and some viral organisms, the neurotropic viruses belonging to the Herpesviridae family do not lend themselves to this approach because the virus exists in an incomplete latent form within the cell nucleus with a brief period of recrudescence when the virion is formed [36] and [37], making detection difficult. Attempts to identify the presence of viruses in the inner ear have generally been based on immunohistochemical examinations for viral antigens [38] and serum viral antibody titres. Arnold and Niedermeyer [32] evaluated the presence of higher IgG antibodies against herpes simplex virus (HSV) in the perilymph of patients with Meniere's disease. This result supported the hypothesis that the herpes simplex virus may play an important role in the aetiopathogenesis of Meniere's disease. Higher titres of IgG against adenovirus (ADV) and varicella zoster virus (VZV) were found in patients with Meniere's disease compared with a control group. These findings support the hypothesis that adenovirus and varicella zoster virus may be important in the development of Meniere's disease [39]. The mechanism by which viral infection can cause Meniere's disease is different, due to the large variability between the viruses and host antigens. First, the viruses must have an affinity for the inner ear structures. Second, viral invasion of the endolymphatic sac is impeded by immunological mechanisms under normal conditions [40]. The antigen may be present at all times but hidden from the host's immune system unless there is an active viral infection. Release or exposure of the virus may occur as a result of cell damage or destruction during viral infection. Such previously sequestered antigens would be recognised as foreign by the host, and the resulting immune response may lead to the production of autoantibodies and possibly to a further cycle of tissue damage through autoimmunity. A possible source of the chemical injury to the labyrinth could be the release of infectious nucleic acids from vestibular nerve terminals following reactivation of the virus in the vestibular ganglion. Such nucleic acids have a level of infectivity unlike that of a live virus, but are neutralised by the release of nucleases by blood components [41]. The hypothesis that Meniere's disease is a viral neuropathy is supported by the significant loss of vestibular ganglion cells compared to age-matched temporal bones [42] and [43]. Reactivation of the latent neurotropic virus is dependent on viral load [44].When the viral load reaches a critical level, reactivation of the virus overcomes the host immune response with the release of viral nucleic acids. Release of such toxic products in the labyrinth causes a labyrinthitis, which eventually leads to fibrosis in the vestibular cistern and endolymphatic hydrops. Recently, direct evidence of viral neuropathy in Meniere's disease has been provided by the transmission electron microscopic observation of viral structures in vestibular ganglion cells excised from a patient with Meniere's disease (Picture 3 and Picture 4) [45] and [46]. The clinical response to antiviral medication indicated that vertigo due to Meniere's disease was relieved in 85–90% of patients. It is not surprising that control of vertigo was not greater than 85–90%, as mutant strains of the herpes virus group would be resistant to the acyclovir class of antivirals. Until newer antivirals are developed, approximately 10% of Meniere's disease patients with vertigo will not be controlled. The auditory symptoms are less effectively treated by the antiviral approach because loss of hair cells and spiral ganglion cells secondary to the toxicity of viral proteins in the perilymph is not reversible.
Most of the abstracts are older than this one which was done in 2012. The date is not as relevant as the content. This abstract site numerous studies to back up their conclusion which back up what we on the forums already know and believe, so hopefully this will help Doctors if we present it to them to update their thinking and treatment about Meniere's, which would absolutely help us and anyone with MM.
Hello, I'm wondering, if one starts taking anti-virals as a treatment for MM, does this mean that they are to be taken for the rest of one's life? To me this doesn't make any sense at all, but I am still working through this whole thing. If anyone has any comments, please advise. Thanks!
since there is no cure for HSV or any drug that will kill a virus, you can opt to stay on the maintenance does of an antiviral long term or not. But the virus most likely will become active again at a given time. antivirals suppress the virus which in turn suppresses MM symptoms. But it does not kill viruses You can search for the forums for the studies showing the safety and efficacy of antiviral long term use.