Otolith dysfunction during vertiginous attacks in Ménière's disease

OBJECTIVE: Vertiginous attacks of Ménière's disease (MD) are characterized by various types of vertigo, namely rotatory vertigo, dizziness and drop attack. When a patient complains of dizziness without spontaneous nystagmus, otolith dysfunction cannot be ruled out. The purpose of this study was to evaluate otolith dysfunction during vertiginous attacks of MD or delayed endolymphatic hydrops. MATERIAL AND METHODS: Vestibular function tests were carried out daily for several days in 11 patients (MD, n = 9; delayed endolymphatic hydrops, n = 2) during vertiginous attacks. Otolith function was evaluated by means of the static torsional position of both eyes [static ocular torsion (OT)] whilst in an upright position. We defined otolith dysfunction as an abnormal change (range) in OT without spontaneous nystagmus or as an abnormal change in OT without a change in spontaneous nystagmus. RESULTS: Four patients had an abnormal change (range) in OT without spontaneous nystagmus or an abnormal change in OT without a change in spontaneous nystagmus during vertiginous attacks of MD. CONCLUSIONS: Otolith dysfunction occurs in patients during vertiginous attacks of MD. In cases of ataxia without spontaneous nystagmus, otolith dysfunction most likely causes atypical attacks of MD.     

Otolith Dysfunction During Vertiginous Attacks in Ménière's Disease

Objective—Vertiginous attacks of Ménière's disease (MD) are characterized by various types of vertigo, namely rotatory vertigo, dizziness and drop attack. When a patient complains of dizziness without spontaneous nystagmus, otolith dysfunction cannot be ruled out. The purpose of this study was to evaluate otolith dysfunction during vertiginous attacks of MD or delayed endolymphatic hydrops.

Material and Methods—Vestibular function tests were carried out daily for several days in 11 patients (MD, n = 9; delayed endolymphatic hydrops, n = 2) during vertiginous attacks. Otolith function was evaluated by means of the static torsional position of both eyes [static ocular torsion (OT)] whilst in an upright position. We defined otolith dysfunction as an abnormal change (range) in OT without spontaneous nystagmus or as an abnormal change in OT without a change in spontaneous nystagmus.

Results—Four patients had an abnormal change (range) in OT without spontaneous nystagmus or an abnormal change in OT without a change in spontaneous nystagmus during vertiginous attacks of MD.

Conclusions—Otolith dysfunction occurs in patients during vertiginous attacks of MD. In cases of ataxia without spontaneous nystagmus, otolith dysfunction most likely causes atypical attacks of MD.     

Causal therapy for diseases of the inner ear? (author's transl)]

The examples of sudden deafness and Meniere's Disease are used to discuss the possibilities of causal therapy for inner ear dysfunctions. In sudden deafness, etiological and therapeutic considerations are focused on the problem of disorders of the arterial and venous microcirculation, contributing to oxygen deprivation of the organ of Corti. Disruption of the arterial microcirculation leads to irreversible damage of the sensory organ within minutes and non-responsiveness to therapy, whereas even serious venous circulation disturbances can be treated successfully within days after onset of the acute disease. While knowledge of pathological changes in sudden deafness is still limited, temporal bone studies in Meniere's disease provides important information on its pathogenesis. Many authors have described enlargement of the cochlear duct as evidence for endolymphatic hydrops. Maximum enlargement of the endolymphatic system disrupts the membrane system which separates endo- from perolymph, and can be confirmed by histologic examination. This indicates that a change of the ionic concentration in the inner ear fluids is responsible for inner ear dysfunction. Thus, the acute Meniere attack can be explained as a consequence of the "burst hydrops." Because of the still unknown etiology of hydrops, only its consequences can be treated at the present time: i.c., immediate removal of the toxic potassium concentration from the perilymph by increasing the microcirculation of the inner ear before irreversible damage occurs.     

Pathophysiology of endolymphatic hydrops.

Endolymphatic hydrops of the nonprogressive type occurs in response to a single traumatic or toxic insult of limited duration and although it may result in permanent deficits in sensorineural function, there is total subsidence of vestibular symptoms. Endolymphatic hydrops of the progressive type, on the other hand, appears to be the result of permanent impairment of endolymph resorption and is caused principally by disorders of the endolymphatic sac. It occurs in Menière's disease, syphilitic labyrinthitis and the delayed hydrops syndrome. In addition to deafness of varying extent, it is characterized by episodic vertigo and sometimes by Hennebert's sign. Histological studies suggest that the acute vertiginous episodes are caused by potassium intoxication following ruptures of the membranous labyrinth and that Hennerbert's sign is caused by vestibular fibrosis.     

内淋巴囊同种抗原免疫致自身免疫性Mnière病的实验研究

采用同种粗制内耳抗原（CIEAg）在已致敏的豚鼠内淋巴囊（ES）局部免疫，诱发出明显的前庭和听觉功能障碍，以及与Meniere病极为相似的内耳膜迷路水肿改变。从而证明ES局部同种内耳抗原免疫是一种有效的造成Meniere病的方法，揭示部分Meniere病的发病机制可能与自身免疫因素有关。     

内耳上皮钠通道、水通道蛋白与内淋巴代谢相关性的研究进展

梅尼埃病的主要病理表现为膜迷路积水,但膜迷路积水的具体作用机制尚未完全明确。已有研究证实,膜迷路积水与内耳离子、水转运通道息息相关。对内耳上皮钠通道(ENaC)、水通道蛋白(AQPs)与内淋巴代谢相关性的研究进行综述,探讨膜迷路积水形成机制,为进一步研究梅尼埃病的发病机制和治疗提供科学依据。     

Prognosis of low-tone sudden deafness - does it inevitably progress to Meniere's disease?

CONCLUSION: We conclude that not all low-tone sudden deafness (SD) patients suffered from endolymphatic hydrops even if they had vertigo attack at the onset and that electrocochleography (ECochG) was a useful prognostic tool. OBJECTIVES: To investigate whether low-tone SD was a precursor of Meniere's disease and whether patients with low-tone SD suffered from endolymphatic hydrops. PATIENTS AND METHODS: This was a retrospective case review in the university hospital. A total of 184 patients with low-tone SD were divided into two groups with single and recurrent episodes. The progress, follow-up audiograms, and ECochG results of the patients were reviewed and compared with those of patients with high-tone SD and Meniere's disease. RESULTS: In all, 83 of 177 patients with low-tone SD unaccompanied by vertigo had recurrent hearing loss; 15 of the 83 developed vertiginous attacks. The remaining 94 patients had a single episode. Three of the seven patients with low-tone SD accompanied by vertigo had recurrent hearing loss; two of the three were subsequently confirmed to have Meniere's disease. The other four had a single episode. No difference in rate of progress from SD to Meniere's disease was observed among the low-tone and the high-tone SD groups. The average -SP/AP of each group with a single episode is smaller than that of other groups with recurrent episodes and Meniere's disease.     

Endolymphatic hydrops in patients with vestibular migraine and auditory symptoms

Vertigo patients exhibiting features of vestibular migraine (VM) and Menière’s disease (MD) present a difficult diagnostic challenge to the clinician, and the two entities are likely to overlap. The aim of the present study was to investigate the occurrence of endolymphatic hydrops in patients with VM and auditory symptoms. This was an observatory diagnostic study. At an academic interdisciplinary dizziness centre, nineteen consecutive patients with definite or probable VM and auditory symptoms were examined by locally enhanced inner ear MR imaging. MR images were evaluated for the presence of endolymphatic hydrops. Of the 19 included patients, four patients (21 %) demonstrated evidence of cochlear and vestibular endolymphatic hydrops on locally enhanced inner ear MR imaging (three with “definite VM”, one with “probable VM”). Locally enhanced inner ear MR imaging may be useful in the diagnostic evaluation of patients with VM and auditory symptoms, as some of these patients have signs of endolymphatic hydrops. Whether these patients suffer from MD only and are misdiagnosed as VM or suffer from both, VM and MD or whether endolymphatic hydrops is a consequence of inner ear damage due to VM are clinically relevant questions that can be evaluated by application of this technique.     

In vivo visualization of endolymphatic hydrops in guinea pigs: magnetic resonance imaging evaluation at 4.7 tesla

In order to find out whether it is possible to visualize experimental endolymphatic hydrops in the cochlea with magnetic resonance imaging (MRI) at 4.7 T, we used 11 guinea pigs. Five normal guinea pigs were used as controls. Early manifestation of endolymphatic hydrops was evaluated in endolymphatic sac (ES)-intact animals (n = 6), and advanced manifestation in ES-damaged animals (n = 5) by means of MRI with gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd-DTPA-BMA) contrast agent. Hearing was tested with electrocochleography. The surface area of 3 partitions of the cochlea was used to quantify endolymphatic hydrops. The fine structure of the 3 partitions of the cochlea was visualized with MRI in all animals, as Gd-DTPA-BMA appeared mainly in the scala tympani and scala vestibuli. As early as 5 days after endolymphatic sac surgery, endolymphatic hydrops started to appear as visualized by MRI and also verified with histology. Severe damage to the inner ear barrier with Gd-DTPA-BMA leakage into the scala media was detected with MRI in 1 ES-damaged animal that had a 60-dB hearing loss. To conclude, endolymphatic hydrops can be visualized with high-resolution MRI by means of Gd-DTPA-BMA, and it is possible to quantify the extent of endolymphatic hydrops. Damage to the inner ear barrier or possible rupture of membranes can be shown with the assistance of Gd-DTPA-BMA.     

Delayed endolymphatic hydrops as a clinical entity

Delayed endolymphatic hydrops (DEH) is a clinical entity that can be differentiated from Ménière's disease and is typically observed in patients who have been suffering from longstanding unilateral profound inner-ear hearing loss. DEH probably is caused by delayed atrophy or fibrous obliteration of the endolymphatic resorptive system of the membranous labyrinth. The time that elapses between the occurrence of hearing loss and the onset of DEH can range from 1 to 74 years. The most common cause of hearing loss preceding DEH is juvenile-onset unilateral profound deafness (early childhood unilateral profound sensorineural hearing loss of unknown etiology), followed by labyrinthitis from various causes and physical and acoustic traumas to the inner ear. Two types of DEH exist: the ipsilateral type, in which the ear with profound hearing loss suffers progressive endolymphatic hydrops, and the contralateral type, in which the formation of progressive endolymphatic hydrops takes place in the ear opposite to the previously deafened ear. The incidence of the ipsilateral type is higher than that of the contralateral type, and the contralateral type is more common in older patients. When recurrent episodic vertigo cannot be remedied through conservative treatment, labyrinthectomy and vestibular neurectomy on the deaf ear are curative for ipsilateral DEH. However, no such surgical treatment is available for the contralateral type.     

Acute inner ear deafness]

Sudden inner ear hearing loss initially might suggest a psychogenic disorder of hearing, particularly when it is bilateral and simultaneous. The differential diagnosis includes disseminated encephalitis, syphilitic labyrinthitis and Cogan's syndrome. The history and cause of acute bilateral deafness in meningitis are easy to recognise. Furthermore, unilateral acute inner ear deafness should not be regarded as idiopathic without further consideration. A acoustic neuroma is a possible cause even of a low-tone hearing loss. More controversial is rupture of the round window membrane as a cause of sudden deafness. The deafness after epidemic parotitis obviously leads to a total unilateral hearing loss in every case. Even labyrinthine apoplexy with loss of hearing and vestibular function can be caused by a tumour of the cerebellopontine angle. Idiopathic sudden deafness should be defined as an acute sensory hearing loss whose anatomical basis in an acute vascular endolymphatic hydrops of unknown cause. The sudden deafness affects only one ear; tinnitus and brief vertigo can be accompanying symptoms. A sudden hearing disorder due to other causes should be distinguished from idiopathic lesions.     

Acute low tone sensorineural hearing loss caused by inner ear barotrauma

Three cases of inner ear barotrauma with subjective symptoms and hearing impairment which were similar to the low tone sudden deafness were reported. Case 1 was a 34-year-old man who developed a hearing loss in the next morning of taking an airplane and recovered four days after. Case 2 was a 42-year-old man who developed a hearing loss 2 days after flying in an airplane and hearing loss have recurred 4 times in his right ear for 3 months. Eight months after recovery of previous recurrent attack, a hearing loss occurred in his left ear without flying and recurred twice for 3 weeks. Case 3 was a 25-year-old woman who developed a hearing loss in the right ear after 24 meter depth scuba diving and recurred 4 times for 40 days. Those three patients complained of no vertigo at any attacks and were treated conservatively. From previous reports and the onset and the course of hearing disturbance, acute low tone sensorineural hearing loss in case 1 and case 2 was thought to be caused by circulatory disturbance of the inner ear and in case 3 thought to be caused by inner ear window rupture. But, endolymphatic hydrops was also needed to be take into account in those three cases as a common possible cause. Inner ear barotrauma and so called labyrinthine window rupture were considered to be one of the diseases needed to differentiate from low tone sudden deafness without reference to mono-attack type or recurrent type.     

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.     

Vestibular type of Mondini anomalies with BPPV and Meniere's disease-like symptoms

An extremely rare case with labyrinthine anomaly with normal hearing was demonstrated. This case firstly showed transient positioning vertigo like benign paroxysmal positional vertigo (BPPV) and subsequently episodic vertigo like Meniere's disease. A 55-year-old male attended our hospital, complaining of transient but persistent positioning vertigo in 2004. The apogeotropic positioning nystagmus was observed in spine position. In 2005, he came to feel episodic vertigo continuously for more than 30min like Meniere's disease. We examined CT scan and 3D-MRI, indicating the hypoplastic lateral semicircular canal (L-SCC) fused together with enlarged vestibule on the left side. We finally diagnosed this case as Mondini anomaly on the left side. The imaging analysis is the most useful for differential diagnosis of Mondini anomalies, because symptoms in these patients are actually various due to the individual inner ear condition. The mechanism of generation of BPPV-like vertigo: the otolith in deformed utricle might be transferred into the fused space with vestibule and L-SCC, resulting in the irrigation of the hypoplastic cupula. The mechanism of generation of Meniere's disease-like vertigo: neuro-otologic findings with furosemide test implied endolymphatic hydrops on the left side. Meniere's disease-like episodic vertigo could be due to subsequently generated endolymphatic hydrops.     

Cell proliferation in the endolymphatic sac in situ after the rat Waldeyer ring equivalent immunostimulation

OBJECTIVES/HYPOTHESIS: It has been recognized that immunological mechanisms could be involved in the pathogenesis of different inner ear disorders, such as progressive sensorineural hearing loss, Meniere's disease, and even sudden deafness. The endolymphatic sac acts as an immune control organ for the inner ear and has been considered as an effector site of the mucosa-associated lymphoid tissue. The purpose of the study was to determine the potentially immunological relationship between endolymphatic sac and Waldeyer ring equivalent, one of the most important affector organs in mucosa-associated lymphoid tissue. STUDY DESIGN: Animal model. METHODS: Thirty-six rats were employed. Two animals were killed for histological observation of Waldeyer ring equivalent, and another 34 animals were randomly divided into experimental and control groups and received bilateral intranasal immunizations with keyhole limpet hemocyanin or Freund adjuvant, respectively. The ears of immunized animals and control animals were examined for keyhole limpet hemocyanin-positive memory cells and immunoglobulin G-positive plasma cells with the technique of immunohistochemical analysis. The histopathological changes and cell proliferation in those ears were also assessed. RESULTS: There were paired and organized lymphoid tissues in the lateral wall of the first choana in the rat. Keyhole limpet hemocyanin-positive lymphocytes appeared within the endolymphatic sac at 3 days after the first anti-genetic stimulus of the Waldeyer ring equivalent. Endolymphatic hydrops in the cochlea, elevated amounts of immunocompetent cells, and increased activity of cell proliferation within the endolymphatic sac were also considered after four intranasal injections of keyhole limpet hemocyanin. CONCLUSION: Presumably, endolymphatic sac is supplied with immunocompetent cells from Waldeyer ring equivalent and has an ability of co-reaction with Waldeyer ring equivalent.     

Prevention of vertigo in Ménière's syndrome by means of transtympanic ventilation tubes

The insertion of a transtympanic ventilation tube prevented the occurrence of vertiginous attacks in 82% of a series of 28 patients suffering typical Ménière's syndrome with incapacitating vertigo resistant to medical treatment. The follow-up time exceeds 2 years for all cases. It ranges from 2 to 4 years with an average of 2.5 years. This treatment had no effect on drop attacks. Also, hearing loss does not seem to be influenced. The presence of a transtympanic ventilation tube has not caused any major complications in these patients. Obstruction or loss of the tube was in some cases followed by the reappearance of vertigo. It is therefore important to check the patency of the tube before concluding that treatment has failed. The apparent benefit of ventilation tubes in reducing the occurrence of vertiginous attacks suggests that patients with endolymphatic hydrops are particularly sensitive to middle ear pressure.     

Image evaluation of endolymphatic space in fluctuating hearing loss without vertigo

The objective of the present study was to investigate endolymphatic space images in patients with fluctuating hearing loss without vertigo, and to elucidate its underlying pathophysiology. Eight patients with fluctuating hearing loss without vertigo were included in this study. 3T MRI was taken, 24 h after intratympanic injection of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). Electrocochleography and VEMP tests were performed to evaluate cochlear and vestibular functions. Endolymphatic hydrops were observed both in the cochlea and in the vestibule of all eight patients. Three patients out of six whose summating potential/action potential (SP/AP) ratio was recordable showed an elevation of SP/AP ratio. In the two patients with remarkable endolymphatic hydrops in the vestibule, VEMP was absent from the affected ear. In conclusion, 3T MRI after intratympanic injection of Gd-DTPA revealed endolymphatic hydrops both in the cochlea and in the vestibule in the patients with fluctuating hearing loss without vertigo.     

The exacerbation of symptoms in Menière's disease during the premenstrual period.

The pathophysiology of the characteristic episodic symptoms of vertigo, low-frequency hearing loss, and tinnitus in Menière's disease remains poorly understood. It is likely that the manifestation of this condition may be multifactorial and related to elements affecting the inner ear beyond the underlying pathology of endolymphatic hydrops. We have identified a subgroup of female patients with Menière's disease in which the symptoms of this disorder are correlated with the late luteal phase of the menstrual cycle (premenstrual period). Through audiometric and vestibular testing, we have documented these inner ear effects in six women. Although many hormonal effects occur during the premenstrual period, compartmental fluid redistribution within the body may be the most pertinent. Endolymphatic hydrops represents a fluid imbalance within the inner ear and, when combined with an additional fluid shift, may produce symptomatic dysfunction. Case histories demonstrating the correlation of the symptoms of Menière's disease and the premenstrual period will be presented along with theoretical mechanisms of pathophysiology.     

A high jugular bulb and poor development of perivestibular aqueductal air cells are not the cause of endolymphatic hydrops in patients with Ménière’s disease

Objective

The presence of endolymphatic hydrops in the inner ear, which can be detected with gadolinium-enhanced magnetic resonance imaging (Gd-MRI), is widely recognized as the main pathological cause of Ménière’s disease (MD). However, the precise mechanisms underlying the development of endolymphatic hydrops remains unclear. One hypothesis proposes a relationship between the presence of a high jugular bulb (HJB) and MD, which disrupts the vestibular aqueduct leading to the development of endolymphatic hydrops. This study sought to identify anatomical features in MD patients using computed tomography (CT) images of the temporal bone.

Effects of Intratympanic Injection of Isosorbide on the Vestibular Function of Animal Models of Endolymphatic Hydrops

ObjectivesThe aims of this study were to investigate the effects of intratympanic injections of isosorbide on vestibular function in animal models of endolymphatic hydrops and to find a new treatment option for the acute onset of vertigo in Ménière disease (MD).MethodsSeventy male guinea pigs received intratympanic injection of isosorbide (IT-ISB). The animals were divided into three study groups: control, a chronic hydrops model, and an acute hydrops model. Intracochlear drug concentrations were measured using high-performance liquid chromatography. Vestibular function was analyzed using an animal rotator test with bidirectional sinusoidal harmonic acceleration before and after IT-ISB administration. Histological changes were also investigated.ResultsISB successfully permeated the perilymph through the round window membrane (RWM) at all three concentrations (25%, 50%, and 100%). In the chronic hydrops model, while IT-ISB histologically induced a reduction of endolymphatic hydrops, vestibular function was unchanged. In the acute hydrops model, no endolymphatic hydrops was histologically observed, and vestibular symmetry was also preserved after IT-ISB.ConclusionISB passed through the RWM into the perilymphatic space even at lower concentrations. IT-ISB histologically reduced hydrops in the chronic model and preserved symmetrical vestibular function in the acute model. IT-ISB could be a treatment candidate for acute attacks of vertigo in MD.