Histologic changes after semicircular canal occlusion in guinea pigs.

HYPOTHESIS: Histologic changes occurring after varying degrees of surgical trauma to the inner ear in guinea pigs can reveal the mechanism of hearing preservation/loss. BACKGROUND: Surgical approaches to the inner ear that allow for hearing preservation have gained increasing acceptance in neurotologic surgery. The mechanisms responsible for hearing preservation and hearing loss after partial labyrinthectomy are as yet poorly understood. METHODS: Ten animals underwent semicircular canal occlusion, suctioning of perilymph, ampullectomy, or wide vestibulotomy. Tone-burst auditory brain stem response (ABR) thresholds were performed at weekly intervals after surgery. After 4 weeks, temporal bone specimens were processed to obtain 10-jim sections from plastic-embedded ears. The histologic findings were correlated with the initial and final ABR thresholds. RESULTS: After surgical occlusion of one or more semicircular canals, ABR thresholds were preserved, as the authors reported previously. Suctioning of inner ear fluid led to transient loss of thresholds with recovery. Ampullectomy produced dichotomous results, with some subjects preserving auditory function and others losing auditory function. Wide vestibulotomy resulted in permanent loss of auditory function in most cases. Histologically, there was intraluminal fibrosis and inflammation near the site of surgical entry. Most specimens showed normal cochlear architecture and hair cell counts, irrespective of the degree of hearing loss. Vestibular hair cells were also well preserved, even when they were close to the site of surgical injury. CONCLUSIONS: These findings suggest that electromechanical changes, rather than cell death, are responsible for changes in auditory and vestibular function after partial labyrinthectomy.     

应用微波技术行后半规管阻塞术的实验研究

目的 :探讨应用微波技术行后半规管阻塞术的可行性。方法 :应用微波技术对 2 0只豚鼠行后半规管阻塞术 ,观察术前、术后豚鼠眼震电图 (ENG) ,听性脑干反应 (ABR)及形态学的变化。结果 :术后第 1天豚鼠正弦摆动刺激时术侧眼震反应减弱 ;术后第 3天双侧眼震恢复对称 ;术后 30 d冰水实验结果显示两耳能引出对称性眼震 ;术后 ABR阈值无明显改变 ;术后 6 0 d病理切片证实后半规管完全阻塞而耳蜗 Corti器和壶腹嵴正常。结论 :应用微波技术行后半规管阻塞术是对后半规管阻塞术的一种有意义的改进方法。     

Experimental endolymphatic hydrops and its relief by interrupting the lateral semicircular duct in guinea pigs.

It has been demonstrated that endolymphatic hydrops can be produced in guinea pigs by obliteration of the endolymphatic sac and this phenomenon was reproduced in our own laboratory. Interruption of the lateral semicircular duct of animals with labyrinthine hydrops produced a diminution of the hydrops in 4 out of 8 cases, and these did not show any collapse in the cochlear duct. It was considered that the hydrops was diminished by drainage of the surplus endolymph into the perilymphatic space, and that the cochlear duct was kept secure from collapse because of its distance from the operated lateral semicircular duct and of the utriculo-endolymphatic valve. Persistence of hydrops in the other four cases was thought to be due to closure of the operated lateral semicircular duct or to labyrinthitis. Although this series is not comprehensive enough, it seems to indicate that interruption of the lateral semicircular duct has a possibility of diminishing labyrinthine hydrops, as in cases of Ménière's disease, without hearing disturbance, provided that complications do not develop. Further investigation with many more animals, for a longer period of time after the operation, is required to gain more precisely detailed information.     

Effect of urea on endolymphatic hydrops in guinea pigs

The morphological changes of the inner ear were observed after intravenous administration of 2 g/kg of urea to the guinea pigs with endolymphatic hydrops which had previously been produced by injecting 10% silver nitrate solution into the endolymphatic sac. They showed membranous collapse extensively in the saccule, moderately in the lower turns of the cochlea and less in the upper turns and the utricle. Because of these changes, it is reasonable to assume that urea is causing the endolymph to be reabsorbed in the endolymphatic duct. Furthermore, the effect of urea seemed to depend on the pathological condition of the duct which sometimes showed a varying degree of atrophied change after silver nitrate injection.     

Single cochlear fibre responses in guinea pigs with long-term endolymphatic hydrops

Some cochlear fibre response properties have been measured in two GPs approximately one year after induction of endolymphatic hydrops (by surgical obliteration of the endolymphatic sac and duct). These animals are considered as models of the effects of hydrops in Menière's disease, and the purpose of the study was to examine any modifications of fibre response properties which may underly auditory symptoms of the disease in man. Neurones towards more apical cochlear regions (with low characteristic frequencies) showed the greatest deterioration in tuning properties; on average, in the 1–6 kHz range, Q_10dB values were reduced by a factor of two compared with normal animals. Discharge rate versus intensity functions of such units were abnormally steep, with dynamic ranges reduced by 10–20 dB. Towards higher frequency regions neurone response properties showed less deterioration (contrasting with many other types of cochlear pathology where, in general, the high frequency basal region exhibits greatest vulnerability). We have also observed in a few units an abnormal bursting in both spontaneous and driven discharge. Interspike intervals during bursts are less than 1 ms (within relative refractory period). These findings are related to the auditory symptoms of Meniere's disease, in particular, poor frequency selectivity, loudness recruitment and tinnitus.     

Saccular and cochlear endolymphatic potentials in experimentally induced endolymphatic hydrops of guinea pigs

Saccular and cochlear endolymphatic potentials (SEP and CEP) were recorded in 33 normal animals. We confirmed that SEP is not produced in the saccule per se, but is a potential leak from the cochlea. CEP was reduced to one-tenth of the original value when it reached the saccule. Endolymphatic hydrops was provoked in 32 animals, and CEP and SEP were successfully recorded in 29 and 20 cases, respectively. The measurements were performed in the 2nd, 4th and 12th postoperative week. Both CEP and SEP decreased in magnitude as time elapsed after the surgery. This reduction is attributed to the strial dysfunction. In advanced hydrops, CEP transmission to the saccule is greatly inhibited. It is concluded that the saccular dysfunction can occur in the hydropic ear.     

Effect on brainstem auditory evoked responses of posterior semicircular canal occlusion in guinea pigs

The site of origin of benign paroxysmal positional vertigo is the posterior semicircular canal and when persistent, the condition is known as cupulolithiasis. Singular neurectomy is the current procedure of choice for the treatment of incapacitating cupulolithiasis. The neurectomy is difficult to learn and carries a significant risk of hearing loss. An alternative procedure, whereby the posterior canal is occluded, is discussed. This was performed on 11 guinea pigs and the effect on hearing was measured using brainstem evoked audiometry. Eight animals showed no hearing loss while the other three had a mild to moderate loss of hearing due to intra-operative complications. The effect of canal plugging on hearing compares favorably with the hearing results obtained with singular neurectomy. Posterior semicircular canal occlusion is suggested as a safer and technically easier treatment for incapacitating cupulolithiasis.     

Results of trapezoid rotation test in guinea pigs with unilateral endolymphatic hydrops

Obliteration of the right endolymphatic sac was performed by Kimura's method in 57 guinea pigs with normal hearing and vestibular function. However, 43 animals exhibited postoperative cerebellopontile disturbance and labyrinthitis detected by gait test, ABR test and histological examination. The remaining 14 guinea pigs were evaluated periodically by the trapezoid rotation test. Two weeks after the operation, 11 of these 14 guinea pigs exhibited prolonged right beating nystagmus based on the labyrinthine preponderance of impaired side (Lpi). In addition, endolymphatic hydrops was histological detected in the labyrinth on the operation side. A positive relation was observed between the degree of endolymphatic hydrops and the degree of Lpi. Lpi at 4 weeks after the operation was markedly lower than that at 2 weeks (P = 0.05). Therefore, the degree of Lpi was thought to be influenced by the rate of hydrops development. These results corresponded with the clinical findings that the degree of Lpi increases prior to vertiginous episodes in Meniere's patients.     

Electrophysiological measures of cochlear function in guinea pigs with long-term endolymphatic hydrops

Experimental endolymphatic hydrops was induced in guinea pigs by obliteration of the endolymphtic sac and duct. From 3 to 24 months after this operation, cochlear action potential (AP) audiograms and AP tuning curves were measured. The purpose of this study was to establish parallels, if any, between this supposed animal model of Menière's disease and the auditory symptoms of the disease in man. In some animals, low and middle frequency AP threshold elevations were observed whilst higher frequency regions maintained normal sensitivity. Other animals developed flat or very gradually sloping AP audiograms. These patterns are qualitatively similar to those found clinically in Menière's disease. AP tuning curves measured in frequency regions of threshold elevation indicated a deterioration of cochlear frequency selectivity; psychophysical and electrocochleographic studies demonstrate related changes in Menière's patients. One animal exhibited modifications in AP thresholds and tuning as a result of glycerol administration. These observations improve our confidence in the validity of this animal model for further studies of the pathophysiology of Menière's disease.     

Important factors for the hearing loss caused by the triple semicircular canal occlusion in guinea pigs.

HYPOTHESIS: Dynamic recording of the auditory brainstem response is helpful in verifying harmful procedure(s) to hearing during triple semicircular canal occlusion (TSCO) surgery. The damage to the membranous semicircular labyrinth is the single major contributor to hearing loss caused by TSCO. BACKGROUND: Posterior semicircular canal occlusion has been recognized as an efficient method of eliminating vertigo without causing a significant hearing impairment. Recently, TSCO has also been explored for its potential to treat vertigo of various causes. In limited animal studies, varied hearing impairments have been documented after TSCO. However, the major factor(s) causing hearing loss in TSCO is/are unclear. METHODS: Triple semicircular canal occlusion was performed on 36 guinea pigs in total. The cochlear function of the guinea pigs was monitored by observing the auditory brainstem response. The impact of membranous labyrinth damage on hearing was verified by a between-group comparison. RESULTS: Hearing loss during TSCO was accumulated in every step of semicircular canal manipulation. Generally, perilymph leak was found to cause a slight hearing loss that was predominately recovered during surgery. However, transaction of the membranous labyrinth usually caused a more significant hearing loss that was not recovered during the surgery. In addition, the magnitude of hearing loss seemed to be increased with the elongation of the surgery. However, the hearing can be largely recovered after the surgery even in animals with transaction of the membranous labyrinth. CONCLUSION: Hearing loss caused by TSCO can be greatly reduced by avoiding damage to the membranous labyrinth and by shortening the operation time.     

The quantification of endolymphatic hydrops in an experimental animal model with guinea pigs

To better quantify endolymphatic hydrops in experimental guinea pigs, endolymphatic hydrops was induced by endolymphatic sac obliteration through an extradural posterior cranial fossa approach in the right ear. The area of the scala vestibuli and scala media of each turn on both cochlear midmodiolar sections was measured, using an automated computer-aided design (AutoCAD R14) software combined with a digital camera. No endolymphatic hydrops was observed in all nonoperated ears; however, various degrees of hydrops were present in all operated ears. The average maximum SMA (scala media area) ratio in the 4-week group (2.22 +/- 0.20) was greater than that in the control group (1.10 +/- 0.06). The average maximum SMA ratio of the 8-week group (4.04 +/- 0.52) was greater than that of the 4-week group (p < 0.05). This study provides a reliable methodologic base for the experimental study of Ménière's disease.     

Vestibular hydrops in patients with semicircular canal malformation

ObjectiveTo investigate the vestibular endolymphatic hydrops in patients with semicircular canal malformation.MethodsWe searched 7864 patients who underwent MR Imaging after contrast injection and found 21 patients with semicircular canal malformations. Another 9 non-malformed patients with unilateral hearing loss were randomly included. We asked patients about their medical history and measured the volume of total vestibular fluid space and endolymphatic space. The vestibular volume ratio = endolymphatic space/total fluid space × 100.ResultsHearing loss was observed in 18 of 30 malformed ears and in 7 of 12 non-malformed ears. Statistical analysis showed no association between semicircular canal malformation and hearing loss. In the semicircular canal malformation group, the average vestibular volume ratio (22.6%) in the ears with hearing loss was higher than that in the ears without hearing loss (11.4%). There was no statistically significant difference in the average vestibular %EL in ears with hearing loss between the malformed inner ear group (22.6%) and non-malformed group (28.2%) (P>0.05).ConclusionThere was no correlation between semicircular canal malformation and hearing loss. The mean vestibular hydrops volume ratio of the semicircular canal deformed ears with hearing loss was about 22.6%, which was not different from that of normal ears.     

内耳开窗术对豚鼠耳蜗电图和膜迷路水肿的影响

目的 通过比较耳蜗电图CAP阈值、SP幅度及组织切片,探讨内耳开窗术对豚鼠听力的影响.方法 将听力正常的5只成年豚鼠的双耳进行配对设计.实验耳在耳蜗鼓岬上行内耳开窗,外接注入生理盐水的微泵,在圆窗膜上放置银球记录电极;对照耳只放置记录电极.分别于术后0,2,4,6天记录耳蜗电图的阈值及SP幅度,比较实验耳和对照耳的差异.结果 实验耳和对照耳的耳蜗电图在8 kHz的CAP阈值、SP幅度无统计学差异(P＞0.05),耳蜗组织切片均未见膜迷路水肿.结论 内耳开窗术对豚鼠听力无影响,不会导致膜迷路水肿,可作为内耳给药的有效途径及动物病理模型建立.     

用4.7特斯拉磁共振成像活体内观测豚鼠实验性内淋巴积水

目的探讨用4.7特斯拉试验用磁共振成像系统能否在豚鼠中检测内淋巴积水.方法20只白色或者杂色豚鼠用于该研究.5只正常豚鼠作为对照组,15只豚鼠用于制作内淋巴积水模型.9只内淋巴囊破坏组中的5只和6只内淋巴囊完整组(与乙状窦游离)动物采用gadolinium(Gd)-DTPA-BMA增强MRI检测内淋巴积水.结果由于Gd-DTPA-BMA主要进入鼓阶和前庭阶,耳蜗的三个阶可在所有动物中由MRI清晰显示.在内淋巴囊完整组,内淋巴囊手术后6天MRI即可检测到内淋巴积水,并且由组织学证实.在内淋巴囊破坏组中的1只动物,因内耳屏障的严重破坏而使Gd-DTPA-BMA快速漏入中阶,MRI可检测到该变化,其听力损失为60dB.结论用Gd-DTPA-BMA增强的高分辨MRI可检测出内淋巴积水,有可能对积水程度进行定量测试.在Gd-DTPA-BMA的帮助下,内耳屏障损伤或可能的膜破裂可以被检出.     

Transmastoid superior semicircular canal occlusion.

OBJECTIVE: The traditional surgical repair for superior semicircular canal dehiscence (SSCD) involves either canal plugging or resurfacing via the middle cranial fossa approach. We describe a novel transmastoid occlusion technique. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Three patients with symptomatic computed tomography-proven SSCD. INTERVENTION: Transmastoid superior semicircular canal occlusion using bone pate in 2 fenestrations, with 1 placed on either side of the dehiscence. MAIN OUTCOME MEASURES: Hearing and vestibular symptoms. RESULTS: Two patients were primary cases of SSCD, and a third patient had failed a previous middle fossa occlusion using fascia at an outside institution. In all 3 cases, the 2 sides of the superior semicircular canal adjacent to the dehiscence were occluded using bone pate, formed from a mix of bone dust and fibrin sealant. This allowed for a permanent bony partition to be achieved between the dehiscence and the remainder of the labyrinth. In all cases, hearing was either preserved or improved, and the procedure was successful in controlling vestibular symptoms. CONCLUSION: Transmastoid superior semicircular canal occlusion is a viable alternative to the customary middle fossa approach for superior canal dehiscence. Meticulous technique and the use of bone pate may help maximize auditory and vestibular results. Advantages of this technique include obviating a craniotomy, preclusion of temporal lobe retraction, familiarity of the approach for experienced otologists, and the ability to occlude the canal without manipulating the defect. The transmastoid approach for superior canal occlusion may not be possible when the dura is low hanging or when there is extensive cranial base dehiscence requiring reconstruction.     

Evaluation of the effect of dexamethasone in experimentally induced endolymphatic hydrops in guinea pigs

PURPOSE: The aim of this study was to investigate the audiological and histopathologic effects of dexamethasone in the treatment of experimentally induced endolymphatic hydrops. MATERIALS AND METHODS: Thirty mature, male guinea pigs weighing 400 +/- 50 g were operated on to induce experimental endolymphatic hydrops in their right ear. Left ear served as control. Subjects were separated into control and dexamethasone groups, with the latter receiving dexamethasone 5 mg/(kg d) intraperitoneally for 10 days. Electrocochleography and auditory brainstem response were applied to all subjects at preoperation, on the second postoperative day and also on the 15th postoperative day in animals that lived for a long time. The histopathologic examination of the inner ear in all animals was done at the end of the study. RESULTS: The summating potential and the ratio of the summating potential to the action potential measured on the second postoperative day were found to be increased in both groups, but more significantly in the control one. When the left and right ears were compared, significant difference was found in the control group; however, no significant difference was found between the ears in the dexamethasone group. Histopathologic examination revealed varying degrees of hydrops in the control group, but showed only normal findings or minor changes in the dexamethasone group. CONCLUSIONS: Dexamethasone can prevent the audiological and histopathologic findings of experimentally induced endolymphatic hydrops. However, these results must be supported by clinical and experimental studies designed with a large number of subjects.     

Mechanisms of development of endolymphatic hydrops following secondary immune response in the endolymphatic sac of guinea pigs]

Previously the author reported the immediate development of endolymphatic hydrops (e. hydrops) following direct challenge of secondary antigen to the endolymphatic sac (ES) in guinea pigs, during the early phases of postchallenge, ranging from 1 to 5 weeks. The present study reports the results of specimens taken up to 10 weeks postchallenge, and correlation of e.hydrops to perilymph in antigen-specific antibody levels. From the present results, mechanisms of e.hydrops induced ES immune reaction are suggested as follows. 1) In the early stage of e.hydrops, an acute inflammatory reaction in the ES may produce endolymph by an increased vascular permeability of the inner ear and may impair endolymph absorption from the ES. 2) In the latter stage of e.hydrops, the moderate cellular infiltration in the ES may cause chronic impairment of endolymph absorption in the ES.     

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

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