Histopathology of the vestibular end organs after intratympanic gentamicin failure for Meniere's disease

CONCLUSION: To our knowledge, this is the first report of the histopathology of the vestibular end organs following intratympanic gentamicin for intractable Meniere's disease. There was relative sparing of the utricular macula, compared with the cristae ampullares. However, the utricular macula exhibited severe hair cell loss. Clinically, the patient has been free from vertigo spells for 3 years following labyrinthectomy. Objective: To describe the histopathology and morphometry of the vestibular end organs from a 59-year-old Meniere's patient who underwent transmastoid labyrinthectomy for recurrent vertigo after failed intratympanic gentamicin. MATERIALS AND METHODS: Light and transmission electron microscopy were utilized; with unbiased stereology-physical fractionator for type I, type II hair cell, and supporting cell counts. Comparison with end organ histopathology in a 56-year-old with Meniere's disease without gentamicin treatment was carried out. RESULTS: Histopathological analysis of the semicircular canal cristae ampullares showed severe atrophy of the neuroepithelium with undifferentiated cells, and fibrosis and edema of the stroma. The utricular macula had some remaining type I and type II vestibular hair cells, and nerve fibers and terminals within the underlying stroma. Morphometric measures were obtained from the utricular macula: 2000 type I and 500 type II hair cells, representing 7.3% of type I hair cells and 4.9% of type II hair cells compared with normative controls, and 24 000 supporting cells were obtained.     

Ultrastructural pathology of the vestibule in patients with acoustic neurinomas: secondarily operated cases after posterior fossa operation

Summary The vestibular sensory epithelia from two patients with acoustic neurinomas were examined ultrastructurally. Both patients had first undergone posterior fossa operations 8 months and 3 years before residual tumors in the acoustic canals were removed by a secondary translabyrinthine operation. Labyrinthine sensory tissues were also removed for microscopic studies. In case 1, the utricular macula and the lateral and anterior cristae were observed, with all sensory epithelia showing fairly normal findings. Myelinated nerve fibers below the sensory epithelia also appeared normal. In case 2, only the utricular macula could be observed. The sensory epithelium showed severe degeneration, disappearing sensory cells and increasing cytoplasmic filaments of both the sensory cell and the supporting cell. Myelinated nerve fibers below the sensory epithelia were only rarely found.Offprint requests to: Y. Yaku     

Effects of systemic and lateral semicircular canal administration of aminoglycosides on normal and hydropic inner ears.

Streptomycin was injected subcutaneously into guinea pigs (n = 12) with unilateral endolymphatic hydrops. In the unoperated ears, sensory cells were degenerated at the basal ends of all cochleas and to varying extents in the vestibular sense organs. Hydropic ears, in contrast, showed greater ototoxicity in the cochlear and saccular sensory cells, while the drug's effect on the utricular and cristae sensory cells was increased, but less remarkable. In another series of normal animals (n = 16), streptomycin was applied to a fenestra of the lateral semicircular canal. Sensory cells of all three canal cristae and utricular macula were degenerated frequently, but the sensory cells of the cochleas were rarely affected. The vestibular lesions resulting from the canal approach were greater than those produced by systemic injection. Comparison with a former gentamicin-lateral canal series revealed very little difference in action of the two drugs. However, in hydropic ears, gentamicin application to the lateral canal produced increased lesions in all sensory cells, particularly in the organ of Corti. Hydropic ears are vulnerable and a greater caution is needed in administering aminoglycosides by both the systemic and the canal route to patients with Meniere's disease.     

实验性头外伤后前庭迷路的组织病理变化

用无依托式头外伤装置，造成豚鼠轻型头外伤模型。痛觉恢复后立即处死６只（Ⅰ组），存活１５天处死５只（Ⅱ组）。颞骨火棉胶包埋，切片光镜观察，见两囊斑病变为大片耳石脱落、斑松解、剥离及感觉上皮空泡化、纤毛区大量球形体。１耳球囊斑脱落耳石靠近连合管。壶腹嵴病变为感觉上皮空泡化，上皮紊乱、松解，纤毛区大量球形体及嵴周嗜碱性颗粒附着。嵴周嗜碱性颗粒附着与嵴顶结石症病理变化一致。表明在头外伤后前庭病变，尤其是两囊斑的损害明显。其继发性病变，如嵴顶结石，连合管堵塞，可能是部分头外伤后听及前庭功能障碍的病理基础。     

Projection of afferents from individual vestibular sense organs to the vestibular nuclei in the pigeon

The projection of individual labyrinthine sensory organs to the brain stem was studied by autoradiography, employing discrete [3H]leucine injections into the sensory epithelia. Within the vestibular nuclei, separate partly overlapping termination areas for each end organ were found in the superior and descending vestibular nuclei, whereas projection territories in the medial, ventrolateral and tangential nuclei overlapped extensively. A few lagenar fibres terminated in the external cuneate nucleus. Semicircular canals and utricular macula also project to the lateral cerebellar nucleus and the reticular formation. For each semicircular canal a projection system could be traced to distinct subgroups of the extraocular motoneuron pools.     

Quantitative study of the vestibular sensory epithelium in cochleosaccular dysplasia.

BACKGROUND: Cochleosaccular dysplasia is the most common pathologic finding seen in children with profound congenital sensorineural hearing loss. There has been no quantitative study on the peripheral vestibular system in cochleosaccular dysplasia. OBJECTIVE: To investigate quantitatively the extent of pathologic changes of the vestibular sensory epithelium in cochleosaccular dysplasia. SUBJECTS AND METHODS: Thirteen temporal bones with congenital deafness from 10 individuals were selected for this study from the temporal bone collection of University of Minnesota that showed suitable pathologic findings for the histopathologic criteria of cochleosaccular dysplasia. Age-matched normal control temporal bones were also selected. The vestibular hair cells including types I and II hair cells were counted separately in the saccular macula, utricular macula, and three cristae of the semicircular canals using Nomarski microscopy. RESULTS: The hair cell densities of types I and II hair cells in the macula of the saccule in cochleosaccular dysplasia were significantly decreased compared with the data of normal subjects. Both types I and II hair cells in the utricular macula and the cristae of the three semicircular canals in cochleosaccular dysplasia were well preserved, and no significant difference was observed between findings of cochleosaccular dysplasia and normal controls in the utricle and the three semicircular canals. CONCLUSIONS: In cases with cochleosaccular dysplasia, the neurosensorial hair cells of the saccule were affected; however, the osseous labyrinth, the membranous utricle, and the semicircular canals were normal. Further studies should be performed to establish the pathogenesis of cochleosaccular dysplasia in humans.     

Superior canal dehiscence reveals concomitant unilateral utricular loss (UUL)

Conclusion: We report enhanced symmetrical cervical vestibular evoked myogenic potential (cVEMP) but asymmetrical ocular VEMP (oVEMP) responses in a patient with CT-verified bilateral superior semicircular canal dehiscence (SCD) but with acute vestibular syndrome. This implies that absence of unilateral utricular macula function alone is sufficient to cause symptoms of acute vertigo. Acute vertigo should not automatically be presumed to originate from semicircular canal dysfunction. Objectives: To identify the cause of an acute vertigo attack in a patient with bilateral SCD. Methods: The functional state of all peripheral vestibular sense organs was tested using the video head impulse test (vHIT) for all semicircular canals and VEMPs to air-conducted sound (ACS) or bone-conducted vibration (BCV) to test all otolith organs. The cVEMP tested mainly saccular function and the oVEMP mainly utricular function. Results: All semicircular canals showed normal function. The cVEMPs showed enhanced, but symmetrical saccular function. In contrast, oVEMPs showed an enhanced but asymmetric n10 component – it was greatly reduced beneath the left eye, implying decreased function in the right utricular macula. That result was confirmed using very high frequency stimuli which are effective in SCD: 4000 Hz BCV stimuli showed that oVEMP n10 was present beneath the right eye but absent beneath the left eye.     

Recurrent benign paroxysmal positional vertigo in two DFNB16 siblings: A CARE case report

IntroductionDeletions or variants of the STRC gene coding for stereocilin cause congenital bilateral mild-to-moderate sensorineural hearing loss without vestibular disorder: DFNB16. Stereocilin is a protein present in vestibular kinocilia embedded in the otoconial membrane of the utricular macula. Benign paroxysmal positional vertigo (BPPV) is a rare form of vertigo in children. The present study reports recurrent positional vertigo in two DFNB16 siblings.ObservationTwo patients, 10 and 15 years old, presented with recurrent disabling positional vertigo episodes, triggered by turning over in bed, with a falling sensation. The diagnosis of right posterior canal BPPV was confirmed on Dix-Hallpike maneuvers in one of the patients. Variations in the response of ocular vestibular-evoked myogenic potentials were observed. Probable BPPV was diagnosed in the second patient. Their other two siblings did not have hearing loss or vertigo.ConclusionThe absence of stereocilin due to homozygous deletions of the STRC gene in DFNB16 patients can cause vestibular dysfunction, including BPPV.     

Vestibulotixoci effect of alkylating agents.

The vestibular sensory epithelia from 3 patients treated with cytotoxic drugs were studied with a surface specimen technique, 2 cases had been treated with cyclophosphamide and 1 with melphalan. In all 3 cases there was some slight degeneration affecting the cristae ampullares. The macula utriculi showed no signs of degeneration. The degeneration affecting the cristae is probably too slight to produce any serious symptoms from the vestibular apparatus.     

Is substance P the neurotransmitter in the vestibular end organs?

The vestibular end organs of the rabbit were fixed intracardially with phosphate buffered 4% formaldehyde, sectioned for 15 micron cryostat sections and incubated with monoclonal substance P (SP) antibody. Specific SP-like immunoreactivity (SPLI) was observed within and below the sensory epithelia of both utricular and saccular maculae and ampullary cristae. Particularly strong SPLI was seen in the maculae which showed many SPLI-positive axons in the subepithelial space and a network of SPLI-positive structures in the basal zones of the sensory epithelium. The calyceal terminals of type I hair cells showed regularly SPLI. The possibility of a transmitter or modulator role for SP in the vestibular function is suggested.     

Vestibular sympathetic nervous system in guinea pig

The vestibular sympathetic fibers were examined in 20 guinea pigs by the immunohistochemical demonstration of tyrosine hydroxylase and dopamine B-hydroxylase. The vestibular sympathetics originated in the ipsilateral superior cervical ganglion and entered the internal auditory meatus along the labyrinthine artery. At the Schwann-glial border, some of the sympathetic fibers left the artery and went into the superior and inferior divisions of the vestibular nerve and formed a loose meshwork among the Scarpa's ganglion cells, while other fibers continued to follow the labyrinthine artery. Both groups of fibers entered the cristae ampullares and saccular and utricular maculas after several bifurcations in the cribrose areas and terminated either near the capillaries beneath the sensory epithelia or among the vestibular nerve fibers. These fibers traveled freely in the vestibular labyrinth without being restricted to following blood vessels or vestibular nerve fibers. Some sympathetic fibers made direct contact with the vestibular efferent fibers or the vestibular afferent fibers at the node of Ranvier. Sympathetic fibers were not observed in the sensory epithelia or semicircular canals, and were rarely found in the vicinity of the dark cells.     

Total deafness from aminoglycoside overdosage: histopathologic case study

A 57-year-old patient became totally deaf two days after receiving excessive doses of the aminoglycosidic antibiotic lividomycin parenterally for 14 days; she died four and a half months later. Her temporal bones were examined by microdissection, surface preparation, and serial sectioning of the modiolus. Loss of inner and outer cochlear hair cells was virtually complete. Refractile concretions were scattered along the atrophic stria vascularis, especially in the middle turn. The distal half of the radial cochlear nerve fibers in the osseous spiral lamina had degenerated, but closer to the modiolus they appeared to be intact. The spiral ganglion in the basal turn showed partial loss of neurons. Scanning electron microscopy revealed hair cell loss from the vestibular end-organs, more severe in the ampullar cristae than in the utricular macula. The dark cells of the utricular wall appeared to be altered.     

Smad4 条件基因敲除小鼠前庭终器形态学研究

目的研究Smad4条件基因敲除小鼠前庭终器形忿改变，探讨Smad4基因对于前庭发育的作用。方法利用建立的Smad4条件基测敲除小鼠模型．通过光镜观察Smad4（＋／＋）、Smad4（＋／-）与Smad4（-／-）三种基因型小鼠（0．5、1．5月龄）的球囊及囊斑、椭圆囊及囊斑、半规管及壶腹嵴、前庭神经节、内淋巴管与囊的形态结构、毛细胞的形态及排列缺失情况。通过扫描电镜观察球囊斑、椭圆囊斑和壶腹嵴的形态结构、毛细胞及纤毛的排列缺失情况。结果Smad4（-／-）小鼠个体及内耳明显小于Smad4（＋／＋）和Smad4（＋／-），而后面二者区别不大。所有小鼠的球囊及囊斑、椭圆囊及囊斑、半规管、前庭神经节、内淋巴管与囊的大小和结构正常，淋巴囊腔饱满，囊斑处的感觉上皮、耳石、毛细胞及纤毛排列整齐，没有发现明显的病变．三个基因型间没有差异。Smad4（-／-）小鼠壶腹嵴囊性变多且严重、后半规管壶腹嵴出现明显的副嵴、偶尔可见壶腹嵴感觉上皮空泡样变。壶腹嵴的毛细胞和支持细胞排列整齐，形态无明显改变，未见缺失。扫描电镜示球囊斑、椭圆囊斑、后、外、上半规管壶腹嵴正常，三个基因型之间没有差异。结论Smad4（-／-）小鼠的前庭终器有轻微病理改变，Smad4（＋／＋）与Smad4（＋／-）小鼠的前庭终器形态结构基本正常．表明Smad4对于前庭终器的发育影响可能不明显。     

Are vestibular sensory cells preserved after destruction of Scarpa's ganglion? A study based on metastatic tumors of temporal bone.

OBJECTIVE: The contribution of nerve fibers to the maintenance of vestibular sensory cells is a controversial issue in previous studies using animals and has not yet been studied in humans. The authors investigated this issue by observing vestibular end organs in the temporal bone of three patients in whom the internal auditory canal was infiltrated with tumor cells, and Scarpa's ganglion cells showed complete degeneration. STUDY DESIGN: Retrospective case review. SETTING: University Hospital, Department of Otolaryngology. PATIENTS: Three patients with malignant metastatic temporal bone tumors. INTERVENTION: We investigated the preservative state of vestibular sensory hair cells with the Scalpa's ganglion was destructed. MAIN OUTCOME MEASURES: Maintenances of vestibular sensory hair cells. RESULTS: We found that sensory cells were intact despite the severe destruction of Scarpa's ganglion cells in two of the patients. CONCLUSION: The findings suggest that human vestibular sensory cells can be maintained for an indefinite period after denervation.     

Impulse noise induced damage in the vestibular end organs of the guinea pig. A light microscopic study

Guinea pigs were exposed to the impulse noise from 90-300 rifle shots (peak 158 dB SPL, maximal energy content at 1.1 kHz). This exposure induced severe cochlear damage. The vestibular end organs also showed damage of varying degree. The ampullary cristae were most severely damaged, but changes were also seen in the utricular and saccular maculae. The changes appear to be primarily mechanical and to result from the effect of the acoustic pressure wave on the vestibular labyrinth.     

Paroxysmal positional vertigo as a complication of osteotome sinus floor elevation

Paroxysmal positional vertigo (PPV) is a high prevalence, vestibular end organ disorder due to the detachment of the utricular otoconia floating in the posterior or lateral semicircular canal. Even though in the majority of cases the etiology of PPV is unknown, it may follow viral infection, vascular disorders and head trauma after different surgical procedures. The aim of this study was to investigate the correlation between PPV and the surgical trauma induced by the vibratory and percussive forces on the upper maxilla during the osteotome sinus floor elevation procedure. We performed a complete otoneurological examination on 146 patients affected by atrophic ridges before and after upper maxilla surgery. Four patients showed a PPV of the posterior semicircular canal controlateral to the implanted side 1 or 2 days after the surgical procedure, which promptly was solved with the Epley re-positioning maneuver. We hypothesize that the surgical trauma, and specifically the pressure exerted by the osteotomes, determines the detachment of the otoliths from the utricular macula while the patient head position, hyper-extended and tilted opposite to the side where the surgeon is working, favors the entry of these free-floating particles in the posterior semicircular canal of the implanted side. Although this disease is rather frequent in the normal population and it is a benign, self-limiting peripheral disorder, it should be considered by the oral surgeon as a possible complication of pre-prosthetic upper maxilla surgery, and the patient should be informed before undergoing surgery.     

Ultrastructural study of the human utricular macula and vestibular nerve in meniére's disease.

The authors have carried out an ultrastructural study of the human utricular macula and the vestibular nerve in the internal acoustic meatus of four patients suffering from Meniere's disease. They confirm the presence of degenerative alterations in the utricular sensory epithelium. The nervous fibers situated in the supporting connective tissue of the neuro-epithelium showed modifications in the Schwann cell cytoplasm and in the arrangement of the myelin sheaths. The same alterations appear in the vestibular nerve in the internal acoustic meatus in 2 of our cases. In the other 2, the vestibular nerve was formed by a granular matrix with several myelin figures in the proximity of possible Schwann cell nucleus debris.     

Peripherin immunoreactivity labels small diameter vestibular 'bouton' afferents in rodents.

Recent morphophysiological studies have described three different subpopulations of vestibular afferents. The purpose of this study was to determine whether peripherin, a 56-kDa type III intermediate filament protein present in small sensory neurons in dorsal root ganglion and spiral ganglion cells, would also label thin vestibular afferents. Peripherin immunohistochemistry was done on vestibular sensory organs (cristae ampullares, utriculi and sacculi) of chinchillas, rats, and mice. In these sensory organs, immunoreactivity was confined to the extrastriolar region of the utriculus and the peripheral region of the crista. The labelled terminals were all boutons, except for an occasional calyx. In vestibular ganglia, immunoreactivity was restricted to small vestibular ganglion cells with thin axons. The immunoreactive central axons of vestibular ganglion cells form narrow bundles as they pass through the caudal spinal trigeminal tract. As they exit this tract, several bundles coalesce to form a single, narrow bundle passing caudally through the ventral part of the lateral vestibular nucleus. Finally, we conclude that all labelled axons and terminals were vestibular afferents rather than efferents, as no immunoreactivity in the vestibular efferent nucleus of the brainstem was observed.     

Input–Output Functions of Vestibular Afferent Responses to Air-Conducted Clicks in Rats

Sound-evoked vestibular myogenic potentials recorded from the sternocleidomastoid muscles (the cervical vestibular-evoked myogenic potential or cVEMP) and the extraocular muscles (the ocular VEMP or oVEMP) have proven useful in clinical assessment of vestibular function. VEMPs are commonly interpreted as a test of saccular function, based on neurophysiological evidence showing activation of saccular afferents by intense acoustic click stimuli. However, recent neurophysiological studies suggest that the clicks used in clinical VEMP tests activate vestibular end organs other than the saccule. To provide the neural basis for interpreting clinical VEMP testing results, the present study examined the extent to which air-conducted clicks differentially activate the various vestibular end organs at several intensities and durations in Sprague–Dawley rats. Single unit recordings were made from 562 vestibular afferents that innervated the otoliths [inferior branch otolith (IO) and superior branch otolith (SO)], the anterior canal (AC), the horizontal canal (HC), and the posterior canal (PC). Clicks higher than 60 dB SL (re-auditory brainstem response threshold) activated both semicircular canal and otolith organ afferents. Clicks at or below 60 dB SL, however, activated only otolith organ afferents. Longer duration clicks evoked larger responses in AC, HC, and SO afferents, but not in IO afferents. Intra-axonal recording and labeling confirmed that sound sensitive vestibular afferents innervated the horizontal and anterior canal cristae as well as the saccular and utricular maculae. Interestingly, all sound sensitive afferents are calyx-bearing fibers. These results demonstrate stimulus-dependent acoustic activation of both semicircular canals and otolith organs, and suggest that sound activation of vestibular end organs other than the saccule should not be ruled out when designing and interpreting clinical VEMP tests.     

Incomplete segregation of endorgan-specific vestibular ganglion cells in mice and rats

The endorgan-specific distribution of vestibular ganglion cells was studied in neonatal and postnatal rats and mice using indocarbocyanine dye (DiI) and dextran amines for retrograde and anterograde labeling. Retrograde DiI tracing from the anterior vertical canal labeled neurons scattered throughout the whole superior vestibular ganglion, with denser labeling at the dorsal and central regions. Horizontal canal neurons were scattered along the dorsoventral axis with more clustering toward the dorsal and ventral poles of this axis. Utricular ganglion cells occupied predominantly the central region of the superior vestibular ganglion. This utricular population overlapped with both the anterior vertical and horizontal canals' ganglion cells. Posterior vertical canal neurons were clustered in the posterior part of the inferior vestibular ganglion. The saccular neurons were distributed in the two parts of the vestibular ganglion, the superior and inferior ganglia. Within the inferior ganglion, the saccular neurons were clustered in the anterior part. In the superior ganglion, the saccular neurons were widely scattered throughout the whole ganglion with more numerous neurons at the posterior half. Small and large neurons were labeled from all endorgans. Examination of the fiber trajectory within the superior division of the vestibular nerve showed no clear lamination of the fibers innervating the different endorgans. These results demonstrate an overlapping pattern between the different populations within the superior ganglion, while in the inferior ganglion, the posterior canal and saccular neurons show tighter clustering but incomplete segregation. This distribution implies that the ganglion cells are assigned for their target during development in a stochastic rather than topographical fashion.