[A new positioning maneuver for treating a subtype of postural unsteadiness - based on a modified model of the utricular macula]. / Ein neues Lagerungsmanöver zur Behandlung einer Form von Schwankschwindel auf der Basis eines modifizierten Modells der Macula utriculi

Objectives: A new method for the treatment of a subtype of postural unsteadiness frequently seen in the medical office is proposed. Ten years of successful practical application and continuous refining of this new treatment lead to the definition of symptom-criteria, which are useful to distinguish patients, who get benefit by this new procedure and to a modified model of the utricular macula. Materials and Methods: In a retrospective collection, the data of 15 patients with postural unsteadiness (mean duration of symptoms 61.7 months) successfully treated with the new maneuver are reported. Before treatment, all patients showed normal results in testing the caloric responses of the labyrinth, normal neurological investigation and no signs for cervical vertigo. Before and after treatment the DHI-score (Dizziness Handicap Index) was achieved by using the German version of the DHI-questionnaire. In all groups before and after treatment balance testing was performed using a posturography platform. Results: Application of the new treatment lead to a significant improvement of the DHI-scores and of the posturographic results (significant reduction of body sway). Discussion: The patients, who were successfully treated by the new maneuver have had presented the same symptoms like patients with a proven utricular dysfunction. This leads to a slightly modified model of the utricular macula. Beyond correctly positioned otoconia in the utricular macula and free otoconia in the endolymphatic utricular space, a third fraction of dysfunctional partially detached otoconia is postulated (causing the unsteadiness). Based on this theory, the single hair-cell with its accompanied otoconium might be the smallest receptor-unit of the macula-organ. This smallest receptor-unit might represent a biological mass-spring-system. According to technical mass-spring-systems used as accelerometers, the different sizes of the otoconia for a distinct direction of acceleration are necessary for covering different frequency-bands. Finally, a many years successfully tested modified variation of the new maneuver for treatment in the medical office and for self-treatment is proposed.

ACF7 is a hair-bundle antecedent, positioned to integrate cuticular plate actin and somatic tubulin.

The precise morphology of the mechanosensitive hair bundle requires seamless integration of actin and microtubule networks. Here, we identify Acf7a (actin crosslinking family protein 7a) as a protein positioned to bridge these distinct cytoskeletal networks in hair cells. By imaging Acf7a-Citrine fusion protein in zebrafish and immunolabeling of vestibular and cochlear mouse hair cells, we show that Acf7a and ACF7 circumscribe, underlie, and are interwoven into the cuticular plate (CP), and they also encircle the basal body of the kinocilium. In cochlear hair cells, ACF7 localization is graded, with the highest concentration near each fonticulus--an area free of F-actin in the region of the CP that contains the basal body. During hair-cell development and regeneration, Acf7a precedes formation of the hair bundle and CP. Finally, electron tomography demonstrates that the ends of microtubules insert into the CP and are decorated with filamentous linkers connecting microtubules to the CP. These observations are consistent with ACF7 being a linker protein, which may shape the cytoskeleton of the hair cell early during hair-bundle genesis.

[Isolated functional loss of the lateral semicircular canal in vestibular neuritis]. / Isolierte Rezeptorfunktionsstörung des horizontalen Bogengangs.

Today, modern tools in vestibular testing are feasible to provide information about functional status of all five peripheral vestibular receptors. Isolated or combined loss of crista and macula receptor function can be determined in the diagnostic process. We describe a seldom case of isolated functional loss of lateral semicircular canal receptor function in a 55-year-old patient. Whereas there was no ispilateral caloric response and video head impulse test revealed a catch-up saccade, air-conducted (AC) cervical and ocular vestibular-evoked myogenic potentials (cVEMP, oVEMP), subjective visual vertical and MRI were normal.

CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects.

Cellular heterogeneity represents a major challenge for regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs). Emerging data suggest superior efficacy of ADRCs as compared to the ex vivo expanded and more homogeneous ADRCs (= ASCs) for indications involving (micro)vascular deficiency, however, it remains unknown which ADRC cell subtypes account for the improvement. Surprisingly, we found regarding erectile dysfunction (ED) that the number of injected CD31+ ADRCs correlated positively with erectile function 12 months after one bolus of autologous ADRCs. Comprehensive in vitro and ex vivo analyses confirmed superior pro-angiogenic and paracrine effects of human CD31+ enriched ADRCs compared to the corresponding CD31- and parent ADRCs. When CD31+, CD31- and ADRCs were co-cultured in aortic ring- and corpus cavernous tube formation assays, the CD31+ ADRCs induced significantly higher tube development. This effect was corroborated using conditioned medium (CM), while quantitative mass spectrometric analysis suggested that this is likely explained by secretory pro-angiogenic proteins including DKK3, ANGPT2, ANAX2 and VIM, all enriched in CD31+ ADRC CM. Single-cell RNA sequencing showed that transcripts of the upregulated and secreted proteins were present in 9 endothelial ADRC subsets including endothelial progenitor cells in the heterogenous non-cultured ADRCs. Our data suggest that the vascular benefit of using ADRCs in regenerative medicine is dictated by CD31+ ADRCs.

Summating potentials from the utricular macula of anaesthetized guinea pigs.

The Summating Potential (SP) was first recorded in the cochlea in the 1950s and represents an objective measure of cochlear hair cell function, in vivo. Despite being a regular tool in hearing research, a similar response has not yet been recorded from the vestibular system. This is mainly due to the lack of experimental techniques available to record electrical vestibular hair cell responses in isolation from the much larger cochlear potentials. Here we demonstrate the first recordings of the vestibular SP, evoked by Bone-Conducted Vibration (BCV) and Air-Conducted Sound (ACS) stimuli, in anaesthetized guinea pigs. Field potential measurements were taken from the basal surface of the utricular macula, and from the facial nerve canal following surgical or chemical ablation of the cochlea. SPs were evoked by stimuli with frequencies above ~200 Hz, and only with moderate to high intensity (~0.005-0.05 g) BCV and ACS (~120-140 dB SPL). Neural blockade abolished the Vestibular short-latency Evoked Potential (VsEP) and Vestibular Nerve Neurophonic (VNN) from the facial nerve canal recordings but did not abolish the vestibular SP nor the vestibular microphonic. Importantly, the vestibular SP was irreversibly abolished from the utricle and facial nerve canal recordings following local gentamicin application, highlighting its hair cell origin. This is the first study to record the Summating Potential from the mammalian vestibular system, in vivo, providing a novel research tool to assess vestibular hair cell function during experimental manipulations and animal models of disease.

Immunohistochemical localization and mRNA expression of aquaporins in the macula utriculi of patients with Meniere's disease and acoustic neuroma.

Meniere's disease is nearly invariably associated with endolymphatic hydrops (the net accumulation of water in the inner ear endolymphatic space). Vestibular maculae utriculi were acquired from patients undergoing surgery for Meniere's disease and acoustic neuroma and from autopsy (subjects with normal hearing and balance). Quantitative immunostaining was conducted with antibodies against aquaporins (AQPs) 1, 4, and 6, Na(+)K(+)ATPase, Na(+)K(+)2Cl co-transporter (NKCC1), and alpha-syntrophin. mRNA was extracted from the surgically acquired utricles from subjects with Meniere's disease and acoustic neuroma to conduct quantitative real-time reverse transcription with polymerase chain reaction for AQP1, AQP4, and AQP6. AQP1 immunoreactivity (-IR) was located in blood vessels and fibrocytes in the underlying stroma, without any apparent alteration in Meniere's specimens when compared with acoustic neuroma and autopsy specimens. AQP4-IR localized to the epithelial basolateral supporting cells in Meniere's disease, acoustic neuroma, and autopsy. In specimens from subjects with Meniere's disease, AQP4-IR was significantly decreased compared with autopsy and acoustic neuroma specimens. AQP6-IR occurred in the sub-apical vestibular supporting cells in acoustic neuroma and autopsy samples. However, in Meniere's disease specimens, AQP6-IR was significantly increased and diffusely redistributed throughout the supporting cell cytoplasm. Na(+)K(+)ATPase, NKCC1, and alpha-syntrophin were expressed within sensory epithelia and were unaltered in Meniere's disease specimens. Expression of AQP1, AQP4, or AQP6 mRNA did not differ in vestibular endorgans from patients with Meniere's disease. Changes in AQP4 (decreased) and AQP6 (increased) expression in Meniere's disease specimens suggest that the supporting cell might be a cellular target.

The utricular macula: qualitative and quantitative analysis using 3-T imaging.

PURPOSE: To identify and measure the mean size of the utricular macula using 3-T imaging. METHODS: One hundred one examinations using a 3-T magnetic resonance scanner and standard temporal bone protocol were performed over a 9-month period. Asymptomatic sides were then retrospectively evaluated using the axial T2-driven equilibrium sequence (0.3-mm slice thickness). We performed the following analyses: (1) reported frequency at which this structure could be identified and (2) calculated the mean size of the utricular macula. RESULTS: The utricular macula was identified in all 101 cases as an ellipsoid area of T2 hypointensity in the utricle. The average anteroposterior x transverse x craniocaudal dimensions were 1.7 x 1.5 x 1.0 mm. CONCLUSIONS: The utricular macula is consistently identified with 3-T imaging in asymptomatic patients.

Values for macular perimetry using the MP-1 microperimeter in normal subjects.

PURPOSE: To establish values for the fixation pattern and macular sensitivity to light in healthy subjects using the MP-1 microperimeter (Nideck Technologies, Vigonza, Italy). METHOD: A prospective study of 37 healthy subjects (age: 19-71 years), approved by the institutional review board. Full-threshold microperimetry of the central 12 degrees of the retina (the macula) was performed prospectively, utilizing 16 points with the MP-1. The fixation stability was simultaneously recorded during microperimetry testing. The relationship between the fixation pattern and light sensitivity with age was calculated using linear regression analysis. RESULTS: Microperimetry was performed on 66 eyes. Total mean sensitivity was 18.33 dB (range: 13.0-19 dB). Mean macular sensitivities at 2 degrees , 4 degrees and 6 degrees as measured by the MP-1 were 18.4+/-2.0, 18.2+/-2.3 and 18.2+/-2.1 dB, respectively. The linear regression analysis revealed a 0.019240, 0.0248 and 0.0285 dB per year age-related decline in mean macular sensitivity at 2 degrees, 4 degrees and 6 degrees from the center of the macula, respectively. The total mean fixation stability values within 2 degrees and 4 degrees were 86 and 96%, respectively. The linear regression analysis also revealed a 0.344% and 0.122% per year decline in age-related fixation stability within 2 degrees and 4 degrees , respectively. There were no statistically significant differences between the median retinal sensitivity or fixation stability values for sex or race in the study. CONCLUSIONS: The MP-1 may be a reliable tool to measure macular sensitivity. Among normal healthy subjects, there was a linear decline in light sensitivity with increasing age.

Damage and functional recovery of the Atlantic cod (Gadus morhua) inner ear hair cells following local injection of gentamicin.

This study addresses the ultrastructural and functional damage and subsequent recovery of the inner ear in the Atlantic cod following intrasaccular gentamicin injection. Inner ear damage was assessed using SEM and measurements of AEP following 250-Hz pure-tone stimuli. Data from gentamicin-treated fish were compared with control (no injection) and sham (injection of saline) fish. Control fish had normal response thresholds associated with well-developed hair cell bundles in their macula sacculi. Sham fish had higher response thresholds compared with control fish during the first week post-intervention, but response thresholds were subsequently normal. Treated fish displayed significant inner ear damage associated with an increased average AEP threshold on the third day following treatment. Thereafter, inner ear tissue displayed signs of progressive regeneration until it was comparable to controls from the 14th day. Response thresholds were similar to those of control fish from the 17th day following treatment. These observations suggest that the macula sacculi of Atlantic cod can regenerate towards a near-complete functional and ultrastructural recovery within 17-21 days following ototoxic gentamicin treatment.

[Functional anatomy of the vestibular nerve]. / Anatomie fonctionnelle du nerf vestibulaire.

The vestibular system detects head movements such as angular rotation, translation, and head position relative to gravity. It acts to stabilize the eyes and posture through subcortical reflexes. Its signals are also integrated at the cortical level to participate in the elaboration of a body scheme, used for different functions such as spatial orientation and motor control. The vestibular nerve shows a resting discharge rate that is modulated up or down according to head motion or position. Central functioning depends on the detection of an asymmetry between signals coming from a pair of peripheral sensors, one on either side. In pathological cases, unilateral peripheral dysfunction is interpreted by the central system as an asymmetry resulting from a change in head position leading to nystagmus, postural disturbances, and vertigo. The dysfunction can be either a deficit, such as observed in vestibular neuronitis, or hyperactivity such as observed in neurovascular compression syndrome of the VIIIth nerve. Anatomically, the VIIIth nerve has a long Root Entry Zone (REZ) that extends over 10mm before entering the brainstem. The VIIIth nerve is also physiologically close to numerous vessels at the pontocerebellar angle and internal auditory meatus. Therefore, vestibular syndrome resulting from neurovascular compression syndrome of the VIIIth nerve may exist, but it is very difficult to prove using radiological imagery.

Otopetrin-2 Immunolocalization in the Human Macula Utricle.

BACKGROUND: In the present study, we investigated the localization of otopetrin-2-a member of the otopetrin family that encodes proton-selective ion channels-in the human macula utricle using immunohistochemistry. METHODS: Macula utricle were acquired at surgery from patients who required transmastoid labyrinthectomy for intractable vertigo due to Meniere's disease (MD; n = 3) and/or vestibular drops attacks (VDA; n = 2) and from temporal bones (n = 2) acquired at autopsy from individuals with no balance disorders. Immunofluorescence staining with otopetrin-2 (rabbit affinity purified polyclonal antibody) and GFAP (mouse monoclonal antibody) to identify vestibular supporting cells was made in formalin fixed cryostat sections or whole microdissected utricle (for flat mount preparations). Secondary antibodies against rabbit and mouse were used for the identification of both proteins. Digital fluorescent images were obtained using a high-resolution laser confocal microscope. RESULTS: Using cryostat sections and flat mount preparations otopetrin-2 immunofluorescence was seen as punctated signal throughout the supporting cells cytoplasm. GFAP immunofluorescence was present in the supporting cell cytoplasm. The distribution of otopetrin-2 was similar in the macula utricle obtained from MD, VDA, or autopsy normative patients. CONCLUSIONS: Otopetrin-2 was localized in supporting cells in a similar fashion that otopetrin-1 previously reported in the mouse macula utricle. The differential expression of otopetrin-2 in the supporting cells of the human macula utricle suggest an important role in the vestibular sensory periphery homeostasis and otolith maintenance.

Resting discharge patterns of macular primary afferents in otoconia-deficient mice.

Vestibular primary afferents in the normal mammal are spontaneously active. The consensus hypothesis states that such discharge patterns are independent of stimulation and depend instead on excitation by vestibular hair cells due to background release of synaptic neurotransmitter. In the case of otoconial sensory receptors, it is difficult to test the independence of resting discharge from natural tonic stimulation by gravity. We examined this question by studying discharge patterns of single vestibular primary afferent neurons in the absence of gravity stimulation using two mutant strains of mice that lack otoconia (OTO-; head tilt, het-Nox3, and tilted, tlt-Otop1). Our findings demonstrated that macular primary afferent neurons exhibit robust resting discharge activity in OTO- mice. Spike interval coefficient of variation (CV = SD/mean spike interval) values reflected both regular and irregular discharge patterns in OTO- mice, and the range of values for rate-normalized CV was similar to mice and other mammals with intact otoconia although there were proportionately fewer irregular fibers. Mean discharge rates were slightly higher in otoconia-deficient strains even after accounting for proportionately fewer irregular fibers [OTO- = 75.4 +/- 31.1(113) vs OTO+ = 68.1 +/- 28.5(143) in sp/s]. These results confirm the hypothesis that resting activity in macular primary afferents occurs in the absence of ambient stimulation. The robust discharge rates are interesting in that they may reflect the presence of a functionally 'up-regulated' tonic excitatory process in the absence of natural sensory stimulation.

Ultrastructural changes in otoconia of osteoporotic rats.

The etiology of benign paroxysmal positional vertigo (BPPV) remains obscure in many cases and women are affected more often than men. A recent prospective study, performed in women >50 years of age suffering from recurrent BPPV, showed associated osteopenia or osteoporosis in a large percentage of these patients. These results suggested the possible relationship between recurrent BPPV and a decreased fixation of calcium in bone in women >50 years. To test this hypothesis, an experimental study was performed in adult female rats. Utricular otoconia of female rats in which osteopenia/osteoporosis was induced by bilateral ovariectomy (OVX) were compared to those of sham-operated adult females rats (SHAM), as control group. FIRST STUDY: The morphology of theutricles of OVX and SHAM rats was analyzed with scanning electron microscopy. In osteopenic/osteoporotic rats, the density of otoconia (i.e. the number of otoconia per unit area) was decreased (p = 0.036)and their size was increased (p = 0.036) compared to the control group. SECOND STUDY: To test the role of calcium turnover in such morphological changes, utricular otoconia of 2 other groups of OVX and SHAM rats, previously injected with calcein subcutaneously, were examined by conventional and epifluorescence microscopy. In epifluorescence microscopy, labeling with calcein showed no significant fluorescence in either group. This finding was interpreted as a lack of external calcium turnover into otoconia of adult female rats. The ultrastructural modifications of otoconia in osteopenic/osteoporotic female adult rats as well as the role of estrogenic receptors in the inner ear are discussed. The possible pathophysiological mechanisms which support the relationship between recurrent BPPV in women and the disturbance of the calcium metabolism of osteopenia/osteoporosis are debated.

Age-related differences in parameters of vestibular evoked myogenic potentials.

CONCLUSIONS: The statistically significant correlations between vestibular evoked myogenic potential (VEMP) parameters and age may be due to hair cell loss of the otolith organ and/or to degenerative changes of the vestibular neural pathway. These findings indicate that age should be taken into account when interpreting VEMP results. It is also important to determine a standard method for performing VEMP and a universal index for comparison among laboratories. OBJECTIVES: VEMP, which measures the surface electric potential from the cervical muscle evoked by sufficiently loud sounds, is a useful tool to evaluate vestibule-colic reflex function. We have assayed the effect of age on VEMP results. SUBJECTS AND METHODS: After excluding subjects with a previous history of dizziness, middle ear pathology, or other inner ear symptoms, a total of 97 healthy volunteers (194 ears) were included. All VEMP parameters were analyzed to find differences related to side and gender, as well as the relationship between age and each VEMP parameter. RESULTS: Age was correlated with all VEMP parameters. Latency of p13, n23 showed a negative correlation and amplitude of p13-n23 showed a positive correlation with age. Differences between the right and left sides were not significant.

A place principle for vertigo.

OBJECTIVE: To provide a road map of the vestibular labyrinth and its innervation leading to a place principle for different forms of vertigo. METHOD: The literature describing the anatomy and physiology of the vestibular system was reviewed. RESULTS: Different forms of vertigo may be determined by the type of sense organ, type of ganglion cell and location in the vestibular nerve. CONCLUSION: Partial lesions (viral) of the vestibular ganglion are manifested as various forms of vertigo.

Dynamic response to sound and vibration of the guinea pig utricular macula, measured in vivo using Laser Doppler Vibrometry.

With the use of a commercially available Laser Doppler Vibrometer (LDV) we have measured the velocity of the surgically exposed utricular macula in the dorsoventral plane, in anaesthetized guinea pigs, during Air Conducted Sound (ACS) or Bone Conducted Vibration (BCV) stimulation. We have also performed simultaneous measurements of otolithic function in the form of the Utricular Microphonic (UM) and the Vestibular short-latency Evoked Potential (VsEP). Based on the level of macular vibration measured with the LDV, the UM was most sensitive to ACS and BCV between 100 and 200 Hz. The phase of the UM relative to the phase of the macular motion was relatively consistent across frequency for ACS stimulation, but varied by several cycles for BCV stimulation, suggesting a different macromechanical mode of utricular receptor activation. Moreover, unlike ACS, BCV evoked substantially distorted UM and macular vibration responses at certain frequencies, most likely due to complex resonances of the skull. Analogous to LDV studies of organ of Corti vibration, this method provides the means to study the dynamic response of the utricular macula whilst simultaneously measuring function.

The role of jab1, a putative downstream effector of the neurotrophic cytokine macrophage migration inhibitory factor (MIF) in zebrafish inner ear hair cell development.

Macrophage migration inhibitory factor (MIF) is a neurotrophic cytokine essential for inner ear hair cell (HC) development and statoacoustic ganglion (SAG) neurite outgrowth, and SAG survival in mouse, chick and zebrafish. Another neurotrophic cytokine, Monocyte chemoattractant protein 1 (MCP1) is known to synergize with MIF; but MCP1 alone is insufficient to support mouse/chick SAG neurite outgrowth or neuronal survival. Because of the relatively short time over which the zebrafish inner ear develops (~30hpf), the living zebrafish embryo is an ideal system to examine mif and mcp1 cytokine pathways and interactions. We used a novel technique: direct delivery of antisense oligonucleotide morpholinos (MOs) into the embryonic zebrafish otocyst to discover downstream effectors of mif as well as to clarify the relationship between mif and mcp1 in inner ear development. MOs for mif, mcp1 and the presumptive mif and mcp1 effector, c-Jun activation domain-binding protein-1 (jab1), were injected and then electroporated into the zebrafish otocyst 25-48hours post fertilization (hpf). We found that although mif is important at early stages (before 30hpf) for auditory macular HC development, jab1 is more critical for vestibular macular HC development before 30hpf. After 30hpf, mcp1 becomes important for HC development in both maculae.

Regeneration of vestibular otolith afferents after ototoxic damage.

Regeneration of receptor cells and subsequent functional recovery after damage in the auditory and vestibular systems of many vertebrates is well known. Spontaneous regeneration of mammalian hair cells does not occur. However, recent approaches provide hope for similar restoration of hearing and balance in humans after loss. Newly regenerated hair cells receive afferent terminal contacts, yet nothing is known about how reinnervation progresses or whether regenerated afferents finally develop normal termination fields. We hypothesized that neural regeneration in the vestibular otolith system would recapitulate the topographic phenotype of afferent innervation so characteristic of normal development. We used an ototoxic agent to produce complete vestibular receptor cell loss and epithelial denervation, and then quantitatively examined afferent regeneration at discrete periods up to 1 year in otolith maculas. Here, we report that bouton, dimorph, and calyx afferents all regenerate slowly at different time epochs, through a progressive temporal sequence. Furthermore, our data suggest that both the hair cells and their innervating afferents transdifferentiate from an early form into more advanced forms during regeneration. Finally, we show that regeneration remarkably recapitulates the topographic organization of afferent macular innervation, comparable with that developed through normative morphogenesis. However, we also show that regenerated terminal morphologies were significantly less complex than normal fibers. Whether these structural fiber changes lead to alterations in afferent responsiveness is unknown. If true, adaptive plasticity in the central neural processing of motion information would be necessitated, because it is known that many vestibular-related behaviors fully recover during regeneration.

Attachment of the utricular and saccular maculae to the temporal bone.

The present investigation concerns the true morphology of the attachment of the two otolith receptor organs the utricular and the saccular maculae in two and three dimensions. By applying a new visualization method, which utilized the application of X-ray microtomography and a method of contrast enhancement based on en-bloc staining in osmium tetroxide, we were able to overcome problems of artefact production such as tissue distortion and loss of valuable information that was present in previous studies. A series of more than 1000 axial sections were obtained for each of the specimens, which subsequently formed the basis for detailed 2D and 3D visualizations. Our interpretations of these data reveal that the saccular maculae are closely attached to the curved bony surface of the temporal bone as traditionally believed, but the utricular macula is attached to the temporal bone only at the anterior region of the macula.

The blood labyrinthine barrier in the human normal and Meniere's disease macula utricle.

The ultrastructural organization of the blood labyrinthine barrier (BLB) was investigated in the human vestibular endorgan, the utricular macula, using postmortem specimens from individuals with documented normal auditory and vestibular function and surgical specimens from patients with intractable Meniere's disease. Transmission electron microscopic analysis of capillaries located in the normal human utricular stroma showed vascular endothelial cells with few pinocytotic vesicles, covered by a smooth and uniform basement membrane surrounded by pericyte processes. Meniere's disease specimens revealed differential ultrastructural pathological changes in the cellular elements of the microvasculature. With moderate degeneration of the BLB, there were numerous vesicles within the vascular endothelial cells (VECs), with increased numbers at the abluminal face, pericyte process detachment and disruption of the perivascular basement membrane surrounding the VECs. With severe degeneration of the BLB, there was severe vacuolization or frank apparent necrosis of VECs and loss of subcellular organelles. A higher severity of BLB degenerative changes was associated with a higher degree of basement membrane thickening and edematous changes within the vestibular stroma. This study presents the first ultrastructural analysis of the capillaries constituting the BLB in the human vestibular macula utricle from normal and Meniere's disease.