Audiological manifestations of allergic rhinitis.

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.

Functional blood flow patterns of the endolymphatic sac in the rat.

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.

A potential portal flow in the inner ear.

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.

The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops.

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.

Endolymphatic sac-vein decompression for intractable Meniere's disease: long term treatment results.

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.

Vascular occlusion in the endolymphatic sac in 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 is associated with that of multidrug resistance protein 1 (MRP1) in the vestibular labyrinth and endolymphatic sac of the guinea pig.

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.

[The submucosal structure of the endolymphatic sac of guinea pigs].

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.

Studies of cochlear blood flow in guinea pigs with endolymphatic hydrops.

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.

Differences between cochlear blood flow and endolymphatic sac blood flow in guinea-pigs.

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.

Localization of nitric oxide synthase isoforms (I, II and III) in the endolymphatic sac of the guinea pig.

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.

[The vascular pattern of the endolymphatic duct, endolymphatic sac and its anatomic differences in guinea pigs].

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.

[Anatomy of the endolymphatic sac and its clinical significance].

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.

The endolymphatic duct and sac of the rat: a histological, ultrastructural, and immunocytochemical investigation.

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.

Degeneration of vestibular sensory cells caused by ablation of the vestibular aqueduct in the gerbil ear.

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.

Expression of intercellular adhesion molecule-1 during inner ear inflammation.

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 blood flow versus cochlear blood flow following intravenous administration of isosorbide in guinea pigs.

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).

Immunoperoxidase study of the endolymphatic sac in Menière's disease.

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.

Arterial supply of the human endolymphatic duct and sac.

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.