Surgical treatment of Meniere's disease and its pathophysiological validation

The authors analyse their own and literature data on surgical treatment of Meniere's disease (MD) as intervention on the endolymphatic sac with assessment of various modifications by long-term results, on sympathetic intraaural and extraaural lesions. Surgical interventions on the endolymphatic sac are pathophysiologically validated. Insufficient knowledge on hydrodynamics in the internal ear labyrinth and the role of endolymphatic hydrops in MD pathogenesis hampers assessment and further development of surgical treatment of the disease. Future lines of the research in Meniere's disease and its treatment are outlined.     

A case of delayed endolymphatic hydrops.

A 30-year-old male with delayed endolymphatic hydrops was given a sac operation. An intradural portion of the endolymphatic sac was resected and the epithelial surface was examined under a scanning electron microscope. The epithelium showed fibrous degeneration and disappearance of the epithelial cells. Pathogenesis of degeneration of the endolymphatic sac is discussed.     

Effects of amiloride on the endolymphatic sac

The effect of amiloride on the murine endolymphatic sac was investigated. The amiloride caused collapse of the lateral intercellular spaces in the endolymphatic sac epithelium and a subsequent mild endolymphatic hydrops. These changes indicated a decreased absorption of endolymph in the endolymphatic sac. Amiloride is known to inhibit the transcellular fluid transport without inducing any changes in the paracellular fluid transport. It is therefore suggested that amiloride specially inhibits the fluid and ion exchange in the apical portion of the epithelial cells resulting a decrease in transcellular fluid transport across the endolymphatic sac epithelium. The transcellular fluid transport seems to be one of the main mechanisms in the endolymphatic sac fluid exchange system.     

内耳上皮钠通道、水通道蛋白与内淋巴代谢相关性的研究进展

梅尼埃病的主要病理表现为膜迷路积水,但膜迷路积水的具体作用机制尚未完全明确。已有研究证实,膜迷路积水与内耳离子、水转运通道息息相关。对内耳上皮钠通道(ENaC)、水通道蛋白(AQPs)与内淋巴代谢相关性的研究进行综述,探讨膜迷路积水形成机制,为进一步研究梅尼埃病的发病机制和治疗提供科学依据。     

The endolymphatic sac in the Mondini disorder

Summary The endolymphatic sacs are described in temporal bone specimens from a 31-year-old man with bilateral Mondini disorder. The ducts and sacs are thin-walled, cyst-like structures with complete absence of loose vascular perisac tissue, and are directly apposed to the bone of the vestibular aqueduct. Histological evidence of severe bone erosion is present in these specimens and is most marked in the intermediate and distal portions of the vestibular aqueduct. It is also present in the foveal region of the posterior temporal bone surface underlying the sac. Erosion of the bony wall of the paravestibular canaliculus (PVC) is demonstrable, with incorporation of the vein of the PVC inside the margin of the widened vestibular aqueduct. These findings suggest a causal relationship between pressure within the endolymphatic duct and sac and erosion of the surrounding bone. The absence of endolymphatic hydrops of the cochlea and vestibular organs in the Mondini disorder constrast significantly with the endolymphatic hydrops seen in Meniere's disease.Supported by The Hope for Hearing Foundation, UCLA     

Pathohistological study on active endolymphatic hydrops in guinea pig--with stress stimulations

Recently Meniere's disease is believed to show a pathological features of endolymphatic hydrops, but the etiology of this disease has not yet been ascertained. Many investigators tried to create animal models with endolymphatic hydrops by obliterating endolymphatic sac and duct. However, these methods have not been adequate to explain the mechanism of development of Meniere's disease, because it gives mechanical damage to destroy endolymphatic sac and duct. On the other hand, Meniere's disease is thought to develop even as a result of stress. The present paper reported the conduction of an acute experiment, creating active endolymphatic hydrops by stress load, to study the occurrence rate of endolymphatic hydrops and the pathological findings of inner ears by a light microscope. This was followed by a light and electron microscopic study on the changes in permeability of the cochlear lateral wall with horseradish peroxidase and a study of the development mechanism of endolymphatic hydrops. Results obtained were as follows: 1. Although it was impossible to cause endolymphatic hydrops with a single stimulation, four kinds of stress stimulations could cause endolymphatic hydrops with the rate of 37.8%. 2. Judging from the different pathological findings between the group with four kinds of stress stimulations and the untreated control group, vessel permeability in the stria vascularis was highly changeable, while that in the spiral ligament was not. 3. It was found out that increased permeability of the stria vascularis vessels was by increased pinocytotic vesicular transport and through tight junctions from vessel lumen to basal lamina and that it was presumably only by increased pinocytotic vesicular transport beyond basal lamina. 4. It was assumed that increased permeability of the stria vascularis vessels was one of the causes of endolymphatic hydrops which were believed to be pathological features of Meniere's disease.     

The vascular supply of the endolymphatic sac.

The vascular anatomy of the endolymphatic sac in guinea pigs was examined following intravascular injection of silicone rubber (Microfil). Methacrylate resin of low viscosity (Mercox) was used to obtain vascular corrosion casts for scanning electron microscopy, which allowed more accurate differentiation between arteries and veins. The extensive vascular system around the sac comprises both arteries and veins, as well as lymphatic vessels. The arterial supply is derived mainly from the posterior meningeal artery in the posterior cranial fossa. In some cases a small artery also leads to the sac from the posterior vestibular artery in the labyrinth (in 7 of the 35 animals investigated). It courses together with the vein of the vestibular aqueduct along the walls of the endolymphatic duct. The blood is drained over the intermediate portion of the endolymphatic sac, which becomes lodged in a rich meshwork of capillaries, venules, veins and a few small arteries. A few venous trunks from both sac walls fuse with the vein of the vestibular aqueduct, which drains blood from the vestibule to the sigmoid sinus. Scanning electron microscopy also revealed numerous anastomosing vessels within bone channels with adjacent bone marrow sinusoids, which also probably contribute to the vascular supply of the endolymphatic sac.     

Ultrastructure of the endolymphatic sac in two-phase endolymphatic hydrops in the guinea pig.

Two-phase endolymphatic hydrops is a subtle experimental model for Meniere's disease. Chronic dysfunction of the endolymphatic sac, induced by dissection of the most distal part without causing damage to the intermediate part, is combined with increased endolymph production induced by administration of aldosterone which stimulates the N/K-ATPase in the stria vascularis. A transmission electron microscopic study was performed on the endolymphatic sacs of four groups of guinea pig cochleas: controls: non-operated aldosterone-treated cochleas; operated (dissection of the endolymphatic sac) cochleas; operated and aldosterone-treated cochleas. Light and electron microscopy showed a normal morphology in the controls. Aldosterone treatment had no visible effect. Dissected ears revealed severe deviations. The epithelium of the intermediate sac was low, showed dilated lateral intercellular spaces indicating elevated fluid transport and displayed serious degenerative processes. Distally, the endolymphatic sac was completely blocked by newly formed bone. Additional aldosterone treatment had no cumulative effect on the dissected ears.     

Induction of experimental endolymphatic hydrops by immunologic techniques

Immunologic techniques have been used by many investigators to produce experimental endolymphatic hydrops models. These techniques, however, have achieved little success in producing models simulating the idiopathic endolymphatic hydrops of Meniere's disease, in which no inflammatory changes occur in the perilymphatic spaces. In this study, the antigen horseradish peroxidase (HRP) was injected into the endolymphatic sacs of ninety guinea pigs that had been systematically sensitized to this antigen. Endolymphatic hydrops was induced in sixty-seven of the subjects, sixty-four of which showed no inflammatory changes in the perilymphatic spaces. The endolymphatic sacs of the affected guinea pigs were packed with soft granulation tissue induced by immunologic mechanisms; it is felt that the hydrops was caused by disturbances in endolymph absorption resulting from these tissue formations. Our results suggest that the introduction of antigens into the endolymphatic sac may prove useful in producing endolymphatic hydrops with characteristics similar to those occurring in Meniere's disease.     

The vascular pattern of the endolymphatic sac in the human embryo

The venous vascular anatomy of the endolymphatic sac in human embryos was examined. The endolymphatic sac was found to be covered by sinusoid-like blood vessels arising from the sigmoid sinus. A rich and extensive capillary network was present on the epithelial surface of the endolymphatic sac. Connections between this capillary bed and the vein in the paravestibular canaliculus were seen. The blood of the endolymphatic sac can therefore drain either into the vein of the vestibular aqueduct in the paravestibular canaliculus or directly into the sigmoid sinus. The vessels lying on the endolymphatic sac are thin-walled and irregular. The endothelial cells lies in direct contact with the epithelial cells of the endolymphatic sac. The reduction of the dense capillary bed in the young embryo to only a few vessels in the order embryo is described.     

Delayed vertigo and profound sensorineural hearing loss

Episodic vertigo, similar to that of Meniere's disease, can occasionally develop years to decades after an ear has suffered a profound sensorineural hearing loss. Although the pathogenesis of this process is unknown, it is theorized that delayed endolymphatic hydrops develops. An inflammatory reaction could cause obstruction of the endolymphatic duct or interfere with venous drainage from the region of the endolymphatic sac, leading to hydrops. This condition is reviewed, and two adult patients with severe episodic vertigo and a unilateral profound sensorineural hearing loss which occurred in childhood are presented. Their evaluation and management are discussed.     

Hypoplastic endolymphatic sac, hydrops, and Mondini deformity: a case report.

The Mondini deformity of the inner ear is usually associated with a large vestibular aqueduct and endolymphatic sac. The authors present a case with a hypoplastic sac and endolymphatic hydrops, which are presumed to be the cause of the Meniere's syndrome symptoms that occurred in mid-life.     

The endolymphatic sac in the Mondini disorder

The endolymphatic sacs are described in temporal bone specimens from a 31-year-old man with bilateral Mondini disorder. The ducts and sacs are thin-walled, cyst-like structures with complete absence of loose vascular perisac tissue, and are directly apposed to the bone of the vestibular aqueduct. Histological evidence of severe bone erosion is present in these specimens and is most marked in the intermediate and distal portions of the vestibular aqueduct. It is also present in the foveal region of the posterior temporal bone surface underlying the sac. Erosion of the bony wall of the paravestibular canaliculus (PVC) is demonstrable, with incorporation of the vein of the PVC inside the margin of the widened vestibular aqueduct. These findings suggest a causal relationship between pressure within the endolymphatic duct and sac and erosion of the surrounding bone. The absence of endolymphatic hydrops of the cochlea and vestibular organs in the Mondini disorder contrast significantly with the endolymphatic hydrops seen in Meniere's disease.     

The development of endolymphatic hydrops following CMV inoculation of the endolymphatic sac

The effect of inoculation of cytomegalovirus (CMV) into the endolymphatic sac was examined in CMV-seronegative and seropositive animals. Seronegative animals developed hearing loss, infection in the epithelial cells of the endolymphatic sac and perisaccular connective tissue, and endolymphatic hydrops. Control animals inoculated with inactivated CMV showed no hearing loss, viral infection, or endolymphatic hydrops. Seropositive animals showed complete protection from hearing loss and viral infection, yet a monocytic infiltrate was seen surrounding the endolymphatic sac. Associated with this localized immune response was mild evidence of endolymphatic hydrops in 40% (2/5) of the animals. Control seropositive animals inoculated with inactivated CMV showed no hearing loss or morphological changes. CMV then, can infect cells of the endolymphatic sac resulting in hearing loss and endolymphatic hydrops. The immune response to CMV in seropositive animals is protective, but is associated with endolymphatic sac inflammation.     

Vestibular aqueduct in Menière's disease and non-Menière's disease with endolymphatic hydrops: a computer aided volumetric study.

The volume of the vestibular aqueduct was studied by a computer-aided volumetric method in 9 temporal bones with endolymphatic hydrops from individuals with Menière's disease (MD), 7 temporal bones with endolymphatic hydrops from individuals without a history of Meniere's disease (non-MD hydrops), and 10 normal temporal bones (controls) to investigate the cause of endolymphatic hydrops in both MD and non-MD hydrops. A hypoplastic vestibular aqueduct was found significantly more often in the MD group than in either the non-MD hydrops group (chi 2-test, chi 2 = 4.063, p less than 0.05) or the control group (chi 2-test, chi 2 = 6.363, p less than 0.05). The difference in volume between the non-MD hydrops group and the control group was not significant. It is speculated that a small vestibular aqueduct (presumably containing a small endolymphatic sac) might be a predisposing factor in Menière's disease. In contrast, in non-MD hydrops, there seems to be no correlation of endolymphatic hydrops with a hypoplastic vestibular aqueduct and endolymphatic sac.     

Endolymphatic hydrops in guinea pigs after cauterizing the sac with silver nitrate

There have been several reports of perisaccular fibrosis of the endolymphatic sac in some autopsied cases of Meniere's disease. We attempted to initiate perisaccular fibrosis of the sac in guinea pigs by injecting a small amount of 10% silver nitrate solution that cauterizes the tissue readily to produce scar, ie, fibrosis. Ninety-nine guinea pigs out of 108 (92%) that were treated with silver nitrate showed the endolymphatic hydrops in varied extent, from slight to profound. The extent of hydrops might depend on the extent of destruction of the sac following the cauterization. The lumen of the sac was sometimes occupied with dense fibrous connective tissue with deposition of black-silver particles in it. The silver nitrate injection method is an easy way to produce endolymphatic hydrops in guinea pigs.     

Development of endolymphatic hydrops following immune response in the endolymphatic sac of the guinea pig.

The present study investigated immune injury associated with endolymphatic hydrops (e.hydrops) following locally mounted immune reaction in the endolymphatic sac (e.sac) of guinea pigs. E.hydrops occurred, progressing rapidly within the first week post secondary Keyhole limpet hemocyanin (KLH) challenge in the e.sac and developed into two phases, acute and chronic. On the other hand, primary KLH challenge of the e.sac, PBS inoculation into the e.sac or intradural secondary KLH challenge were incapable of inducing e.hydrops. These results indicate that reversible and irreversible e.hydrops are induced by the immune response of the e.sac, suggesting that local immunological events of the e.sac may provide an animal model of Meniere's disease.     

Long-term effects of destruction of the endolymphatic sac in a primate species

The endolymphatic sacs of ten vervet monkeys were surgically ablated unilaterally, and the animals were assigned predetermined survival times ranging from 6 months to 5 years. The left and right ears were prepared in anatomical continuity for light microscopic study. Four experimental ears had openings in their membranous labyrinths of unknown etiology and were not considered acceptable for correlative studies. The remaining five experimental ears showed mild cochlear endolymphatic hydrops, which was localized to the apical regions or was more severe in the apical regions than elsewhere. Four ears also showed saccular endolymphatic hydrops. The sensory and neural structures in both experimental and control ears were normal, and none of the control ears showed endolymphatic hydrops. None of the animals developed severe endolymphatic hydrops or the cochleovestibular symptoms that occur in human subjects with Meniere's disease. The results of this experiment indicate that dysfunction of the endolymphatic sac may be a contributing factor, but probably is not the sole cause of Meniere's disease.     

The basic science of Meniere's disease and endolymphatic hydrops

PURPOSE OF REVIEW: Meniere's disease is characterized by the triad of fluctuating hearing loss, episodic vertigo, and tinnitus and by endolymphatic hydrops found on post-mortem examination. The cause of Meniere's disease remains unclear. Numerous factors play a role in the development of hydrops and in the pathogenesis of related cochleovestibular dysfunction. This review highlights recent advances in the understanding of the pathophysiology of symptom development in Meniere's disease by detailing the role of genetics, autoimmunity, endolymphatic fluid homeostasis, excitotoxicity, oxidative stress, and cellular apoptosis. Emphasis is placed on reviewing the newly described animal models that exhibit endolymphatic hydrops. RECENT FINDINGS: Recent evidence suggests that hearing loss might be explained in part by apoptosis of spiral ganglion neurons and that hydrops could represent an epiphenomenon rather than an initiating factor. In addition, the accepted guinea pig model described by Kimura has certain limitations. An animal model that would supplement and in some cases replace the surgically induced model is currently being sought. SUMMARY: These recent advances have expanded our understanding and will allow for the development of targeted therapeutic interventions aimed at preventing the progression oochleovestibular deterioration.     

Scanning electron microscopy of the endolymphatic sac epithelium.

In this study, scanning electron micrographs of the dog endolymphatic sac surface epithelium are presented. According to our morphological findings, three portions were recognized, the proximal, intermediate and distal part. The intermediate or 'rugose' portion was found the most differentiated where two types of cells were identified. These cells were seen to have many of the criteria for fluid absorption and phagocytosis. In man, alteration in the ability of these cells may lead to endolymphatic hydrops.