Search

Background: Allergic rhinitis is associated with excess specific immunoglobulin E. Inner ear involvement (via both cellular and humoral immunity) is poorly understood, but appears to arise from the endolymphatic sac and duct., Aims: To assess the otological and audiological status of patients with allergic rhinitis., Methodology: Thirty allergic rhinitis patients (14 men, 16 women; age 17-45 years, mean 31 years) and 20 controls (12 men, eight women; age 21-42 years, mean 27 years) underwent audiological investigation., Results: All study group patients had sensorineural (rather than conductive) hearing loss, worse at high frequencies. All had abnormal transient evoked otoacoustic emissions and 27 had abnormal distortion product otoacoustic emissions. All had a statistically significantly prolonged wave I latency, and shortened absolute wave I-III and I-V interpeak latencies, compared with controls., Conclusion: Allergic rhinitis patients had a higher prevalence of hearing loss and otoacoustic emission abnormalities than controls. The endolymphatic sac can process antigens and produce its own local antibody response; the resulting inflammatory mediators and toxic products may interfere with hair cell function. Additional research is needed to determine the clinical value of audiometry and otoacoustic emission testing in allergic rhinitis.

Conclusion: Visualization of the endolymphatic sac vascular network under video fluorescence microscopy showed a typical microvascular organization. The microvascular arrangement and the microcirculation may reflect a functional state of the endolymphatic sac. Damage or change of the blood circulation following endolymphatic sac surgery is discussed., Objectives: To visualize and study the dynamic microcirculation of the endolymphatic sac in live rats., Method: An experimental animal study using in vivo video fluorescence microscopy., Results: Visualization of the endolymphatic sac vascular network showed a typical microvascular organization. The endolymphatic sac appeared hypervascular and independent from other vascular systems. The microcirculation of the endolymphatic sac was supplied by ramification of a single artery, while venous trunks perpendicular to the length of the endolymphatic sac served as return paths for the microcirculation. The blood flow pattern was highly variable between rats.

Objectives/hypothesis: The aim of the present study was to visualize the flow direction of blood in the extraosseous part of the vein of the vestibular aqueduct (VVA) and to explore the effect of an induced obstruction in the distal part of the VVA before it merges with the sigmoid sinus. The endolymphatic sac has been implicated as a potential endocrine gland, which venules drain to the VVA. A reversal of the direction of flow in the VVA toward the inner ear could, through vestibular arteriovenous anastomosis, cause portal circulation in the inner ear., Study Design: The authors conducted an experimental animal study using in vivo fluorescence microscopy., Results: Obstructing the distal part of the VVA just before it empties into the sigmoid sinus immediately reverses the flow of blood in the VVA toward the inner ear., Conclusions: After an obstruction of the VVA, the drained venous blood from the endolymphatic sac may enter a portal circulation in the inner ear, which could cause disturbances in the endolymph homeostasis and potentially symptoms as seen in Meniere disease.

In the present study, two experiments were performed to investigate the influence of OPC-31260 on experimentally induced endolymphatic hydrops in guinea pigs and the regulation of aquaporin-2 (AQP2) mRNA expression in the rat inner ear. In morphological studies, the increases in the ratios of the length of Reissner's membrane (IR-L) and the cross-sectional area of the scala media (IR-S) were quantitatively assessed among normal guinea pigs (normal ears) and three groups with hydropic ears: hydropic ears with no infusion (non-infusion hydropic ears), hydropic ears with an infusion of physiological saline into the scala tympani (saline-infused hydropic ears) and hydropic ears with infusion of 0.3% OPC-31260 into the scala tympani (OPC-infused hydropic ears). IR-Ls in the experimental groups were markedly larger than in the normal ear group, but there was no significant difference among the groups of non-infusion hydropic ears, saline-infused hydropic ears and OPC-infused hydropic ears. The IR-Ss of non-infusion hydropic ears and saline-infused hydropic ears (48.8-49.3%) were statistically different from that of normal ears (6.5%) (Dunnet multiple comparison test, P<0.01). However, IR-S of the OPC-infused hydropic ears (-14.8%) was significantly smaller than those of non-infusion hydropic ears and saline-infused hydropic ears (one-way ANOVA, P<0.01). In the quantitative polymerase chain reaction study, a comparison of the ratio of AQP2 and beta-actin mRNA (MAQP2/Mbeta-actin) was made between water-injected and OPC-31260-injected rats. An intravenous injection of OPC-31260 resulted in a significant decrease in MAQP2/Mbeta-actin both in the cochlea and in the endolymphatic sac (t-test, P<0.001). These results indicate that water homeostasis in the inner ear is regulated via the vasopressin-AQP2 system, and that the vasopressin type-2 antagonist OPC-31260 is a promising drug in the treatment of Meniere's disease.

Objectives: We sought to determine the long-term efficacy of endolymphatic sac-vein decompression surgery on patients with classic Meniere's disease., Study Design and Setting: Using the 1995 American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium criteria, starting stage, functional level, vertigo class, and hearing results were addressed. We studied 68 patients with classic Meniere's disease from a tertiary, private otology-neurotology practice. Patient data were gathered by retrospective chart review, questionnaire, and patient interview. All patients underwent endolymphatic sac-vein decompression with an average follow-up period of 55 months., Results: Median functional level before surgery was level 4, improving to level 2 after surgery. Eighty-one percent of patients showed improvement in functional level, 12% remained stable, and 7% declined. Long-term vertigo control was 47% in class A, 25% in class B, 9% in class C, 3% in class D, and 16% in class F. Twenty percent of patients were in hearing stage I Meniere's disease; 31%, stage II; 44%, stage III; and 5%, stage IV. Eighteen percent of patients showed improvement in hearing class, 64% were stable, and 18% declined., Conclusion: Endolymphatic sac-vein decompression surgery is a safe, nondestructive surgical option for Meniere's disease that offers durable control of vertigo and stabilization of hearing for the majority of symptomatic patients., Significance: The beneficial long-term outcome of the endolymphatic sac-vein decompression supports its continued use as a first-line treatment option in intractable Meniere's disease.

In 2 patients with severe Meniere's disease (MD), there was histologic evidence of occlusion of the vein of the vestibular aqueduct (VVA). This finding coincided with total or partial occlusion of numerous small vessels around the endolymphatic sac (ES), flattening of epithelium, extensive perisaccular fibrosis, and signs of new bone formation. Ultrastructural analysis of the occluding material showed foci with dense connective tissue, calcification, lipid deposits, and layers of basement membrane, sometimes concentrically arranged. The exact nature of the occluding material was unknown. In another 2 MD patients, the VVA was not visualized, and the ES vessels showed no signs of occlusion. Seven controls with acoustic schwannoma or meningioma had normal vasculature. The presence of vascular impairment in the ES in MD patients indicated that altered hemodynamics may contribute to the pathogenesis of endolymphatic hydrops and MD.

Expression of p-glycoprotein (p-gp) and multidrug resistance protein 1 (MRP1) was detected in the vestibular labyrinth and endolymphatic sac (ES) of the guinea pig by immunohistochemical staining using anti-p-gp monoclonal antibody (mAb) C219 and anti-MRP mAb MRPr1. P-gp was detected in capillary endothelial cells of the crista ampullaris, utricle, saccule and ES. MRP1 was detected in the epithelial lining of the crista ampullaris, utricle, saccule, and epithelial cells of the ES. Since p-gp and MRP1 act as extrusion pumps, they may coordinate with each other in vestibular organs and ES and play an important role in the blood-labyrinth barrier.

Objective: To investigating the submucosal structure of the endolymphatic sac (ES), so as to analyse the role of ES in the function of inner ear., Method: The temporal bone of the guinea pigs were cleared in methyl salicylate and inspected under a stereomicroscope. The ultrastructure of endolymphatic sac has been observed by transmission electron microscope., Result: The extensive vascular system around the sac and has compact contact with sinus sigmoid. Its submucosal space comprises both arterioles and venules, as well as lymphatic sinus., Conclusion: The result suggests that the ES is a very metabolically active structure and has a pressure regulating function. The disturbance of endolymphatic resorptive function seems to result endolymphatic hydrops after the vascular supply poverty of endolymphtic sac. It's may be the causative factor of Meniere's disease.

Laser Doppler flowmetry was used to assess cochlear blood flow (CoBF) in guinea pigs with experimental endolymphatic hydrops following intravenous infusion of 5 types of drugs: 50% glycerol, 70% isosorbide, 20% mannitol, 7% sodium bicarbonate, and 1% diphenidol. The magnitude of the CoBF changes following infusion tended to be smaller in the hydropic ears than in the normal control ears. A significant reduction in CoBF changes was observed in hydropic ears infused with isosorbide and sodium bicarbonate. These results suggest that the cochlear microvascular sensitivity to various stimuli such as drug infusion is reduced in hydropic ears. This may result from atrophy of the stria vascularis which is often observed in the hydropic ears of guinea pigs. Thus it seems likely that the same reaction occurs in the inner ear of patients with Ménière's disease in whom atrophy of the stria vascularis is also presumed to exist in conjunction with extensive endolymphatic hydrops. Therefore, it seems probable that the function of the microvasculature of the stria vascularis is impaired in the inner ear of patients with Ménière's disease, resulting in the slow progressive deterioration of the inner ear with time.

Cochlear blood flow (CoBF) and endolymphatic sac (ES) blood flow (ESBF) were measured in different groups of guinea-pigs by laser-Doppler flowmetry after the intravenous administration of various drugs through the jugular vein for 60 sec. These drugs included 50% glycerol, 70% isosorbide, 20% mannitol, 7% sodium bicarbonate and 1% diphenidol. For CoBF measurements, a probe was positioned on the basal turn of the right cochlea via a ventral approach. For ESBF measurements, it was placed on the right ES through the posterior cranial fossa via a dorsal approach. The average initial measured value of ESBF (8.31 +/- 2.97 ml/min/100 g) was significantly greater (p < 0.0001) than that of CoBF (4.33 +/- 1.15 ml/min/100 g). Following administration of most drugs except for diphenidol, both CoBF and ESBF increased immediately after administration; however, following diphenidol administration both CoBF and ESBF decreased. The magnitude of the CoBF response tended to be greater than that of the ESBF response (p = 0.006-0.112). It seems likely that this reflects anatomical differences in the vascular supplies, i.e. CoBF from the vertebrobasilar artery and ESBF from the external carotid artery. In addition, the presence of micropores or fenestrations in the ES vasculature may contribute to the differences between CoBF and ESBF.

The localization of nitric oxide (NO) synthase (NOS) isoforms was examined in the endolymphatic sac (ES) of the pigmented guinea pig by indirect immunohistochemistry. The cytoplasm of the epithelial cells in the ES showed both NOS-I and -III immunoreactivity, whereas their nuclei appeared negative. NOS-III staining was also observed in the endothelial lining of the blood vessels. These findings support the hypothesis that NO in the epithelial cells may play an important role for the active intracellular transport of the endolymph and ion. NO may also be crucially involved in the regulation of ES blood flow. Immunostaining for NOS II revealed no reactivity in general, while in lipopolysaccharide-inoculated animals, intense reactivity was found in the cytoplasm of the ES epithelial cells as well as macrophages in the lumen. Thus it has been indicated that NO also may play an important role in the immunodefensive mechanisms in the ES.

In order to study the vascular pattern of the endolymphatic duct and sac, endolymphatic duct and sac were examined with vascular Indian ink injection and image analysis. The Results were as follows: 1. In the 20 temporal bones, 17 (85%) had posterior meningeal artery (PMA) and posterior vestibular artery (PVA) supply and the rest (3 specimens, 15%) had no PVA supply; 2. The distribution frequency of PMA in the endolymphatic sac was much higher than that of PVA(P < 0.01), but the distribution of PMA and PVA in the endolympatic duct were not different (P > 0.05). The conclusions is that there are anatomic differences in vascular supply and pattern of the endolymphatic duct and sac, PMA is the main vascular structure in the endolymphatic sac.

Using 28 formalin fixed temporal bones and materials of 26 cases of endolymphatic surgery for menieres' disease, the location, vascular distribution and size of the endolyphatic sac (ELS) were investigated. ELS were measured with surgical microscope in all the cadaver specimen with a mean length of 6.9393 +/- 2.0429 mm and mean width of 5.8821 +/-1.6522 mm. All the specimens showed no clear capillary distribution. Only in 24 of the 26 ELS surgeries for Menieres' disease the ELS were found. The mean length was 6.8125 +/- 2.2449 mm, the mean width 5.6666 +/- 1.5084 mm and the vascular distribution was unclear in 29% of the cases. It was found that the ELS usually located at the Donaldson line, and moved downward in the under-developed mastoid with smaller size.

A study of the ultrastructure, vascularization, and innervation of the endolymphatic duct and sac of the rat has been performed by means of light- and electron-microscopic and immunocytochemical methods. Two different types of epithelial cells have been identified: the ribosome-rich cell and the mitochondria-rich cell. These two cell types make up the epithelium of the complete endolymphatic duct and sac, although differences in their quantitative distribution exist. The morphology of the ribosome-rich cells varies between the different parts of the endolymphatic duct and sac; the morphology of the mitochondria-rich cells remains constant. According to the epithelial composition, vascularization, and structural organization of the lamina propria, both duct and sac are subdivided into three different parts. A graphic reconstruction of the vascular network supplying the endolymphatic duct and sac shows that the vascular pattern varies among the different parts. In addition, the capillaries of the duct are of the continuous types, whereas those supplying the sac are of the fenestrated type. Nerve fibers do not occur within the epithelium of the endolymphatic duct and sac. A few nerve fibers regularly occur in the subepithelial compartment close to the blood vessels; these fibers have been demonstrated in whole-mount preparations by the application of the neuronal marker protein gene product 9.5. Single beaded fibers immunoreactive to substance P and calcitonin-gene related peptide are observed within the same compartment. Dopamine-beta-hydroxylase-immunoreactive axons are restricted to the walls of arterioles. Morphological differences between the different portions of the endolymphatic duct and sac are discussed with regard to possible roles in fluid absorption and immunocompetence.

The vestibular aqueduct of the gerbil has a unique anatomic feature that makes it possible to selectively obliterate the endolymphatic sac with or without interfering with its venous drainage. In animals in which only the endolymphatic sac was ablated, endolymphatic hydrops was slight in the cochlea and was absent in the vestibular labyrinth. The cochlear and vestibular sensory cells were normal. In animals in which both the endolymphatic duct and the vein were obliterated, hydrops was slight, with the exception of a few cochleas that showed moderate hydrops. The sensory cells of the posterior canal cristae had degenerated in all specimens, while varied pathologic changes in cochlear and vestibular sensory cells were present in some specimens. These results suggest that hydrops is primarily due to blockage of the endolymphatic duct and sac and that degeneration of sensory cells occurs when blood flow in the vestibular aqueduct is impeded. Pathologic changes in the endolymphatic sac, including the vascular plexus at the endolymphatic sac, may play an important role in the production of endolymphatic hydrops and vestibular symptoms in Meniere's disease.

This study was designed to investigate the expression of intercellular adhesion molecule-1 (ICAM-1) on the spiral modiolar vein (SMV) with its collecting venules (CVs) and the venules of the endolymphatic sac during inner ear inflammation. These data will further elucidate the role of adhesion molecules in extravasation of inflammatory cells from blood vessels during an inner ear immune response. Labyrinthitis was induced in rats by inoculation of keyhole limpet hemocyanin into the scala tympani of animals who had been systemically sensitized to it. Expression of ICAM-1 was examined with a mouse monoclonal antibody to rat ICAM-1 by immunohistochemistry. ICAM-1 was found weakly on the epithelium of SMVs and CVs as early as 6 hours postchallenge, reaching a maximum by day 2 and then fading away gradually. The maximum influx of immunocompetent cells into the cochlea was seen between days 3 and 7. Staining for ICAM-1 was observed on the epithelium of the endolymphatic sac and perisaccular region at 12 and 24 hours, respectively, and this was associated with infiltration of cells into these areas 3 days postchallenge. By day 28, the inner ear had developed endolymphatic hydrops, but at this time it showed almost no significant staining with anti-ICAM-1. The molecule was also expressed in the mesothelium of perilymph, the perineurium of cochlear nerves, the spiral ligament, and the basal cells of the stria vascularis following immunization. Our data provide evidence that endothelial cells of the SMV and its CVs, as well as other inner sites, have the potential to express ICAM-1. This expression precedes the influx of immune cells; therefore, it is possible that this ligand plays a pivotal role in the onset of inflammation in the inner ear. This study also confirmed that the immune response results in endolymphatic hydrops as a long-term consequence.

Endolymphatic sac (ES) blood flow (ESBF) and cochlear blood flow (CBF) were measured in different groups of guinea pigs by laser-Doppler flowmetry (Advance Laser Flowmeter, Model ALF 2100) after the intravenous administration of 70% isosorbide (1.6 ml/kg). The measurements were made under general anesthesia with intraperitoneal pentobarbital sodium. Respiration was controlled by a respirator after tracheotomy, and blood pressure was monitored through the femoral artery (Gould Statham P23 ID Pressure Transducer). For ESBF measurements, a probe was placed on the right ES after entering the posterior cranial fossa via the dorsal approach. For CBF measurements, a probe was placed on the basal turn of the right cochlea via the ventral approach. Isosorbide was administered intravenously through the jugular vein for 60 s. Both ESBF and CBF increased immediately after administration, reached a peak within 3-6 min and decreased gradually to their initial baseline levels in 11-15 min. Both blood flow changes almost always corresponded to systemic blood pressure changes, although a slight delay was observed in blood pressure compared to the blood flow. The magnitude of the CBF response tended to be greater than that of the ESBF response (p < 0.1). This may result from the anatomical differences in the two blood supplies, i.e., from the vertebral artery (CBF) and the external carotid artery (ESBF).

A growing body of evidence suggests that some cases of Menière's disease may be mediated by immune mechanisms. Because endolymphatic sac dysfunction is believed to be an underlying cause of Menière's disease, this study used immunohistochemical techniques to demonstrate the presence of immune complex deposition in the sacs of patients with Menière's disease. Positive immunoglobulin G (IgG) staining was noted in 10 of 23 sac biopsies from Menière's patients, with 2 specimens showing perivascular deposition. Only 1 of 5 control specimens was only slightly positive for IgG. Clinical correlation showed a statistically significant increase in disease bilaterality (P < .05), larger summating potential/action potential (SP/AP) ratios with electrocochleography (ECoG), and a tendency toward worse hearing and more progressive disease among the immunopositive Menière's patients. The results provided histological evidence of immune injury in the endolymphatic sacs of patients with Menière's disease.

The arterial anatomy of the endolymphatic duct and sac was studied in vascular casts of methyl methacrylate of six human heads. The chief source of arterial blood supply to the endolymphatic duct and sac appeared to be the occipital artery. Arterioles entered the bone of the mastoid process. Arterioles in bone, the walls of the sigmoid sinus, and the posterior fossa dura coursed medially to supply the endolymphatic sac. The orientation of arterioles tended to be along the long axis of the endolymphatic duct and sac, whereas venules were more likely to be circumferentially oriented. Arterioles arising from dural vessels divided into deeper branches, which supplied periductal connective tissue, and superficial branches, which entered canaliculi of the vestibular aqueduct. Gross anatomic findings were confirmed by histologic examination of temporal bones.

A decrease in vascular density in the endolymphatic sac was suspected as a factor in the pathogenesis of endolymphatic hydrops in Meniere's disease. The present study was undertaken to explore this possibility by cutting the posterior meningeal artery and the sigmoid sinus above and below the external aperture of the vestibular aqueduct or by incision of the dura adjacent to the sinus in 18 guinea pigs. The lesions in the sac were greater in the segmental ablation of the artery and sinus and were consistently associated with the development of endolymphatic hydrops. Among the lesions shown in the sac epithelia, the intermediate portion was most often and most severely affected with a decrease in rugose formation and a flattening of the tall epithelial cells or replacement of epithelial cells by squamous type cells. A high correlation between the lesions in the intermediate portion and occurrence of hydrops suggests that the intermediate portion plays a greater role in the pathogenesis of endolymphatic hydrops. The sac luminal precipitates known to be increased in human Meniere's cases were decreased or absent in this study, which suggests that the increased amount is unlikely to be the cause of endolymphatic hydrops. The evidence supports the hypothesis that these substances are secreted by the endolymphatic sac. The limited sensory cell lesions seen in the cochleae and saccules are likely to be due to a temporary vascular ischemia and endolymphatic hydrops.

The capillary permeability and the basolateral endocytic pathway of the mouse endolymphatic sac (ES) epithelium were examined in vivo using intravenous injection of horseradish peroxidase (HRP). The capillaries of the ES were classified as either fenestrated or non-fenestrated. Because dense reaction products were observed soon after injection of HRP in macrophages near both types of capillaries, they were both considered to be permeable to macromolecules. In non-fenestrated capillaries, the basement membrane and small vesicles of the endothelium of the ES were stained with reaction product. These non-fenestrated capillaries were considered to be of muscle type. After 15 min, ES epithelial cells absorbed HRP basolaterally, and the multivesicular bodies and lysosomes of epithelial cells were stained with reaction product. The process of basolateral absorption in the ES epithelium was similar to that in the intestinal epithelium. Our results provide further evidence that the ES is a metabolically active organ which plays an important role in fluid transport in the inner ear.

The vascular network of the gerbilline endolymphatic sac (ES) and its dynamics were studied using different morphological procedures. The normal condition was compared to serum osmotic alterations induced by changing the daily water intake of the animals. The gross morphology was studied after intracardiac injection of Berlin Blue, while light (LM) and transmission electron microscopy (TEM) were applied for the ultrastructural analysis. A rich vascular supply was seen in the intermediate portion of the normal ES, and the presence of micropores and fenestrations confirmed also in this animal species the importance of this region for fluid exchange. The lacunar arrangement of the vessels in the distal portion of the ES, together with the close vicinity of this area to the bone marrow, led to the hypothesis that the distal ES possesses a functional role as blood reservoir. The hyperosmotic condition induced by water deprivation appeared to affect mostly the morphology of the red cells. In some of the capillaries, a thrombus-like occlusion was also evident. This vascular occlusive condition appeared to be partly reversible when water intake was reestablished, although the morphological alterations induced by the hyperosmotic condition to the subepithelial tissue appeared not to be reversible.

The development of perisaccular blood vessels is described during embryology and the postnatal period of the mouse. Primitive sinusoidal vessels already appear at the early otocyst stage as the future endolymphatic sac is formed. Before birth the vasculature attains a more mature appearance with tubular, somewhat fully developed blood vessels. At this stage a primitive basement membrane is also formed. Soon after birth the blood vessels appear mature with developed fenestrations and micropores, giving them an appearance comparable to blood vessels in other fluid transporting organs.

Histologic and histochemical studies of the endolymphatic sac of full-term rat fetuses were undertaken to clarify the anatomy of the endolymphatic sac, and the mechanism of endolymph circulation and regulation. Hitherto undescribed structure enveloping the sac with blood vessels extending from the sigmoid sinus resembling the kidney glomerulus was seen. This endolymphatic "glomerulus" is believed to provide a means of active exchange of water and electrolytes between blood vessels and the endolymphatic sac.

Unimpeded venous drainage of the vestibular organs via the paravestibular canaliculus (PVC) vein is crucial to inner ear fluid mechanisms. With increased venous pressure, insufficient drainage may result in endolymphatic hydrops, unless collateral veins develop. Different mechanisms cause venous insufficiency in different cases of Meniere's. One suggested mechanism is alteration of the intermediate endolymphatic sac (IES) microcirculation with decreased regulation of blood held within subepithelial capillaries of the sac. Increased blood may thus drain into the veins, with increased venous pressure and inadequate vestibular drainage. Altered microcirculation may be morphological as in fibrosis or shortening of the IES, or physiological where the microcirculation receives abnormal stimuli or reacts abnormally to normal stimuli. Venous insufficiency may result from PVC vein anomalies. Variations in venous pattern whereby vestibular organs preponderantly drain through the PVC vein may predispose to Meniere's disease.

The fenestrated blood vessels surrounding the endolymphatic sac in guinea pigs were investigated with the help of freeze-fracturing. The technique exposes the structure and distribution of vascular pores as well as interendothelial bridges or tight junctions between vascular endothelial cells. It is possible to get a three-dimensional comprehension of the vascular structure which can be compared with that of conventional transmission electron microscopy (TEM). Discontinuity in the junctional elements as seen in some endothelial layers and the high number of fenestrations organized in geometric patterns, as well as the abundant, randomly distributed micropinocytotic vesicles seem to bear out the theory that the endolymphatic sac is one of the most metabolically active parts of the inner ear and may be involved in the turnover of endolymph.

Histologic examination of the temporal bone of a patient with Wegener's granulomatosis showed involvement of the vessels of the endolymphatic sac (ELS) but no involvement of the vasculature of the rest of the inner ear. Autoimmune sensorineural hearing loss in this patient may have been due to interference of antigens and antibodies with the filtering capacity of the ELS, leading to imbalance of inner ear fluids. Histologic findings reemphasize that the cochlea and ELS have different blood supplies.

The vascularity of the endolymphatic sac (ES) in the vestibular aqueduct (VA) and of periaqueductal bony channels was studied in 18 temporal bones from patients with Meniere's disease and in the same number of control bones with no endolymphatic hydrops and no premortem history of otologic disease. The control bones were selected on the basis of having VAs of the same sizes as the hydropic bones. This was important in order to eliminate any possibility that differences in degree of vascularity of the ES could have been due simply to differences in the degree of development of the VA. All specimens were sectioned and stained with hematoxylin and eosin. The ES of each bone was reconstructed two-dimensionally by the medial view graphic reconstruction method, and its vascularity was studied histologically under a light microscope. There were fewer and smaller blood vessels in the ESs of bones from individuals with Meniere's disease than in the ESs of control bones. This was particularly true in the richly rugose and the cranial orifice portions of the sac. However, no significant differences were recognized in the degree of vascularity of the periaqueductal bony channels between control and Meniere's disease bones.

Unilateral endolymphatic hydrops is described associated with absence of the vein in the paravestibular canaliculus (PVC), and with decreased vascularity of the vestibular aqueduct and endolymphatic sac. The venous return from the vestibule was normal as far as the junction of the branches forming the PVC vein. At this junction, a blind venous loop was formed with no continuation of venous drainage through the PVC. This probably represents a developmental anomaly. The decreased vascularity of the endolymphatic sac may be related to the absence of the PVC vein. However, anatomical and functional relationships of these vessels are not clear and need further study. Perisac fibrosis and endosteal bone formation are possibly secondary to the decrease in vascularity. A large chronic rupture of the inferior saccule wall probably accounts for the absence of vertigo and the relatively mild degree of cochlear endolymphatic hydrops.

Animal models of vascular disorders are identified or developed for the evaluation of functional deficits and morphologic alterations. This information will serve a useful purpose for a better understanding of sudden deafness, Meniere's disease, and presbycusis. The study of microcirculation of the inner ear vessels reveals that their responses to various stimuli, such as anoxia, sympathetic nerve stimulation, hypothermia, and drugs, are different from those of the middle ear vessels. In sudden occlusion of the major vascular supply to the inner ear, the cochlea is found to be more vulnerable than the vestibular labyrinth; outer and inner hair cells and stria vascularis are most often affected. Animal models for Meniere's disease are also described, and the importance of vascularity at the endolymphatic duct and sac is discussed from an etiologic viewpoint. In presbycusis, animal models show sensory cell and spiral ganglion cell atrophies in different locations than in human cochleas, and the relationship between these atrophies and vascular impairments is not clear at the present time.

The blood vessels of the vestibule and the endolymphatic duct and sac (ES) of the rat were reproduced with methacrylate casting medium and observed under a scanning electron microscope. Dense capillary networks of the macula utriculi and the macula sacculi were observed. The collecting venules from the vestibule emptied into the vein of the vestibular aqueduct (VVAQ). The plexus of the vessels in the ES was triangular in shape and had anastomoses with vessels of the bone and dura and drained into the VVAQ. The posterior meningeal artery (PMA) gave off two branches to the ES. These findings supported the similarity of the vascularization of the vestibule and the ES between the human and the rat.

A specialized type of blood vessel is demonstrated within the dense soft tissue areas of the vestibular aqueduct and vascular channels of the surrounding bone, including the paravestibular canaliculus (PVC). The vessel wall is formed by the collagen-smooth muscle bundles of these areas. The lumen of these vessels is irregular, and segments appear to be closed by apposition of the bundles. The vessels are continuous with the capillaries of the endolymphatic sac. It is not clear whether they are on the venous side of the capillary system, or on the arterial side and might possibly be part of an arteriovenous anastomoses system. Their possible role in some cases of Meniere's disease must be considered.

Experience based on 14 cases of severe-to-total sensorineural deafness, treated with endolymphatic sac revascularization, operation, is presented. Changes seen in the endolymphatic sacs and lateral sinuses of these patients have been detailed. Irrespective of the degree and duration of deafness, significant hearing gain (with good improvement in speech discrimination) was obtained in nine out of 14 cases (64.28 per cent). There was no improvement at all in one out of 14 (7.14 per cent), and there was a relapse of the hearing-loss two months post-operatively in one case (7.14 per cent). Tinnitus disappeared in the operated ear in three out of five cases (60 per cent) and vertigo improved considerably in four out of six cases (66.66 per cent). The follow-up in this series has been up to two years.

In observing the fine structure of the human endolymphatic sac (ES) by transmission electron microscopy, we defined the cytologic characteristics of the epithelial lining of the various portions of the sac and identified five types of epithelial cells with presumably somewhat different functions. The morphologic findings may suggest that the human ES is involved in endolymph resorption and phagocytosis. In addition, there are indications that in humans the sac may be involved in pressure regulation in the internal ear. The ES has a possible role in the turnover of macular statoconia.

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.

The vein of the vestibular aqueduct (VVA) was investigated in a series of 40 human temporal bones. The processing included vascular injection with a colored medium, decalcification and cutting in serial, thick sections, which were put in a clear fluid and studied with a stereo-microscope. The labyrinthine roots of the VVA are the single veins of the ampulla and simple limbs of the semicircular canals and of the posterior wall of the utricle. They drain the rich capillary bed of the simple endolymphatic walls of the canals and the utricle, as well as a small peripheral area of the cristae and the utricular macula. The VVA leaves the vestibule through an individual bone canal running parallel to the vestibular aqueduct up to the dura of the posterior side of the petrosa in the area of the endolymphatic sac. It then opens in the inferior petrosal sinus or the jugular bulb. The vein receives other branches from the bone, dura and sac. Correct information on the course of this vein appears to be lacking in contemporary textbooks and articles, although it has been correctly described since the last century.

We compared audiometric and clinical histories with findings in temporal bones of eight diabetics and ten normal controls matched for age and sex. The group with diabetes mellitus had significantly more hearing loss than the normal control group (p less than .01). Only patients with diabetes had microangiopathy. Patients with microangiopathic involvement of the endolymphatic sac had significantly greater hearing loss than patients without such involvement (p less than .01). Microangiopathy in the stria vascularis was highly significant in the diabetics (p less than .001); however, they did not have a significant hearing loss. Diabetic patients with basilar membrane microangiopathy had significantly lower percentages of histologically normal hair cells (p less than .05) and stria vascularis cells (p less than .05) and significantly greater hearing loss (p less than .01) than diabetic patients without such pathologic changes. Results of this study suggest that diabetic sensorineural hearing loss results from microangiopathic involvement of the endolymphatic sac and/or basilar membrane vessels.

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.