Long-term effects of middle ear pressure therapy with the EFET01 device in patients with Ménière's disease and delayed endolymphatic hydrops in Japan.

BACKGROUND: Long-term efficacy of middle ear pressure therapy (MEPT) with the EFET01 device in patients in Japan with definitive Ménière's disease (MD) and delayed endolymphatic hydrops (DEH) was evaluated. OBJECTIVE: To examine the effects of reducing vertigo attacks and improving hearing of MD and DEH patients by using MEPT with the EFET01 device for two years after treatment. MATERIAL AND METHODS: A retrospective study was conducted of 32 MD patients and 2 DEH patients treated by MEPT with the EFET01 device from December 2018 to April 2021. According to Japan Society for Equilibrium Research (JSER) guidelines, patients were investigated for the frequency of vertigo attacks and change in hearing levels during a period of 6 months before to 18-24 months after start of treatment. RESULTS: The frequency of vertigo attacks significantly decreased in both MD and DEH patients, and hearing level has remained stable in the majority of our patients after treatment. CONCLUSION: Our study clarified that MEPT with the EFET01 device was effective in controlling vertigo symptoms of MD and DEH. It should be considered a safe option for patients failing medical treatment. SIGNIFICANCE: The efficacy of MEPT with the EFET01 was shown over a 2-year follow-up period.

Progression of endolymphatic hydrops and vertigo during treatment in Meniere's disease.

BACKGROUND: Patients with Meniere's disease (MD) receive treatment to reduce vertigo. PURPOSE: To explore the fluctuation of vertigo symptoms and the changes in endolymphatic hydrops (EHs) in MD patients during long-term regular medication. MATERIALS AND METHODS: We enrolled MD patients who had received two magnetic resonance imaging with intravenous contrast agents. RESULTS: Of the 42 patients in the study, 18(42.9%) had progressive EHs and 3(7.1%) had remission. The change value of the signal intensity ratio (SIR; cochlear perilymph/cerebellum) on the affected side (1.2) was larger than that on the healthy side (0.9), but there was no statistical difference. Among the 30 patients followed up, two patients had complete control of vertigo, two patients had substantial control, and three patients had worse control. The other 23 patients had insignificant control of vertigo symptoms before and after treatment. The correlation between the progression of cochlear and vestibular hydrops and the improvement of vertigo symptoms in MD patients was not significant. CONCLUSIONS AND SIGNIFICANCE: In treated patients with MD, EHs may progress or relieve over the long course of the disease. But there was no correlation between the development of EHs and changes in vertigo symptoms.

12-month effect of middle ear pressure therapy with the EFET01 device for intractable definite Meniere's disease and delayed endolymphatic hydrops after certification by the public health insurance system in Japan.

BACKGROUND: Middle ear pressure therapy (MEPT) is effective for intractable vertigo in patients with definite Meniere's disease (MD) and treatment-refractory delayed endolymphatic hydrops (DEH). Four-month MEPT with the EFET01®, an MEPT device developed in Japan and covered by national health insurance since September 2018, has shown efficacy. However, efficacy and safety after 12 months of treatment, which is appropriate for determining the therapeutic effect of MEPT devices, is unclear. OBJECTIVES: Examine the therapeutic effect of 12-month MEPT using the ETET01®. MATERIAL AND METHODS: Patients underwent MEPT using the EFET01® from September 2018 to July 2021. Thirty-three patients followed for >12 months were enrolled in this retrospective study. Clinical data were evaluated in the first and second 6-month treatment periods. Data from the second 6-month period were compared with data from an MEPT study using a different device. RESULTS: MEPT with the EFET01® significantly improved vertigo in the first period, with further improvement in the second period. The efficacy and safety were comparable to MEPT with other devices. CONCLUSIONS: MEPT with the EFET01® is effective for intractable vertigo in patients with definite MD and DEH, and 12-month follow-up is recommended. SIGNIFICANCE: The efficacy of 12-month MEPT with the EFET01® was demonstrated.

Efficiency of a novel middle ear pressure device for intractable definite Meniere's disease and delayed endolymphatic hydrops after certification by the public health insurance system in Japan.

BACKGROUND: Middle ear pressure therapy (MEPT) is effective in treating intractable vertigo in patients with definite Meniere's disease (MD) and delayed endolymphatic hydrops (DEH) refractory to conservative treatment. A novel middle ear pressure device, the EFET01®, which requires no transtympanic ventilation tubes, was developed in Japan, approved by the Japanese Ministry of Health, Labour and Welfare, and has been used under Japanese national health insurance since September 2018. OBJECTIVES: To examine short-term therapeutic effect of MEPT using the ETET01® compared with previous clinical trial results. METHODS: Patients selected according to Japan Society for Equilibrium Research (JSER) guidelines underwent MEPT using the EFET01 from September 2018 to July 2021, and 44 patients were enrolled in this retrospective study. Clinical data analysed at 4 months after the start of MEPT were compared with those of the previous clinical trial for the EFET01. RESULTS: MEPT using the EFET01 showed the same therapeutic efficacy as that of the previous clinical trial, i.e. improvement in the intensity and frequency of vertigo with no effect on hearing, even under JSER guidelines for proper use of MEPT. CONCLUSION: MEPT using the EFET01 provided an effective treatment option for intractable vertigo in patients with definite MD and DEH.

Long-term effect of transtympanic intermittent pressure therapy using a tympanic membrane massage device for intractable meniere's disease and delayed endolymphatic hydrops.

BACKGROUND: A 12-month follow-up study showed that middle ear pressure treatment with a transtympanic membrane massage (TMM) device had a similar effect to a Meniett device. OBJECTIVES: The effects of pressure treatment with a TMM device were retrospectively compared to the effects of treatment with a Meniett device in patients with Meniere's disease (MD) and delayed endolymphatic hydrops (DEH) who were followed for a minimum of 24 months. MATERIALS AND METHODS: Twenty-seven patients were treated with the TMM device and 14 patients were treated with a Meniett device. The insertion of a transtympanic ventilation tube was necessary for the Meniett device but not for the TMM device. RESULTS: In patients treated with the TMM and Meniett devices, the frequency of vertigo significantly improved at 19-24 months after treatment. The distribution of vertigo at 19-24 months after treatment did not differ between the patients treated with the two types of devices. Pressure treatment for 8 months or more was suitable to achieve remission. CONCLUSIONS AND SIGNIFICANCE: Middle ear pressure treatment for 8 months or more with a TMM or Meniett device was equally effective and provided minimally invasive treatment options for intractable MD and DEH.

Effects of transtympanic intermittent pressure therapy using a new tympanic membrane massage device for intractable Meniere's disease and delayed endolymphatic hydrops: a prospective study.

BACKGROUND: The retrospective study showed that the effect of the middle ear pressure treatment by the tramstympanic membrane massage (TMM) device was similar to that of the Meniett device. OBJECTIVES: The new TMM device named EFET device was prospectively evaluated in patients with Meniere's disease (MD) and delayed endolymphatic hydrops (DEH) and we compared the effects to the Meniett device. MATERIALS AND METHODS: 23 ears of 19 patients were treated with an EFET device, and 17 ears of 15 patients were treated with the Meniett device. All patients suffering from intractable MD and DEH were treated for 4 months. The insertion of a transtympanic ventilation tube was necessary for the Meniett device, but not the EFET device. RESULTS: In patients treated by the EFET and Meniett devices, the frequency of vertigo significantly improved after treatment. The distribution of vertigo outcomes at 4 months after treatment did not differ between patients treated with the both devices. CONCLUSIONS AND SIGNIFICANCE: Middle ear pressure treatment by the EFET device is effective and provides minimally invasive options for intractable MD and DEH like the Meniett device.

The Role of Endolymphatic Hydrops in Patients with Pantonal Idiopathic Sudden Sensorineural Hearing Loss: A Cause or Secondary Reaction.

The purpose of this study was to investigate the presence of endolymphatic hydrops (EH) in both affected and unaffected ears of patients with pantonal unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) using three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) and further evaluate the significance of EH in this disorder. Twenty-seven ISSHL patients were enrolled in this study. 3D-FLAIR MRI was performed 24 h after intratympanic injection of gadolinium-diethylenetriaminepentaacetic acid (Gd-DPTA). The incidences of EH in the affected ears and contralateral unaffected ears were compared and the correlations of EH with vertigo or prognosis were analyzed using the Chi-square test. The results showed that the incidence of EH was 68.0% (17/25) in the affected ears and 34.8% (8/23) in the unaffected ears. There was a statistically significant difference between affected ears and unaffected ears in regard to the incidence of EH (P<0.05). There were no significant correlations of EH with vertigo (P=1.000) or with prognosis (P=0.359) in the affected ears. In conclusion, there is EH in the inner ear of patients with pantonal ISSNHL; EH is not related to vertigo, a concomitant symptom of ISSNHL, and the prognosis of this condition. The presence of EH may be a secondary reaction following the impairment of the inner ears with pantonal ISSNHL.

Fluctuating Sensorineural Hearing Loss.

BACKGROUND: Several otologic conditions can present with fluctuating sensorineural hearing loss, including Ménière's disease, autoimmune inner ear disease, and enlarged vestibular aqueduct. Although these 3 etiologies vary greatly, distinguishing between these conditions at initial presentation can be challenging. Furthermore, initial treatment of these conditions is often similar. In this review, we discuss historical and current perspectives on diagnosis and treatment of these conditions. SUMMARY: A literature search was performed regarding fluctuating hearing loss, and current treatment of these etiologies of fluctuating hearing loss was summarized. Immediate measures at the onset of acute hearing loss include corticosteroid therapy, while preventative and chronic therapies, which can limit disease severity and frequency, vary based on the specific condition treated. Key Messages: Fluctuating hearing loss can represent a range of pathologies, but the precise etiology may not be clear at initial presentation. Timely treatment and long-term follow-up, along with appropriate diagnostics, are necessary to optimize long-term hearing.

Relationship between changes in hearing function and volumes of endolymphatic hydrops after endolymphatic sac drainage.

Background: Endolymphatic sac drainage (ELSD) may have a positive effect on endolymphatic hydrops (EH) and may help to preserve inner ear function. However, the relationship between changes in EH volumes and hearing function after ELSD has not been described. Objectives: We aimed to reveal the factors related to changes in hearing and EH following ELSD. Material and Methods: Twenty-one patients who received ELSD were enrolled. Pure tone audiometry and 3-T magnetic resonance imaging (MRI) 4 h after intravenous injection of gadolinium enhancement were performed just before surgery and 2 years later. To characterize the endolymphatic space (ELS), we measured the volume of the total fluid (TFS) and ELS and calculated the ratio of ELS to TFS (ELS ratio). Results: The ELS ratio of the patients who showed hearing improvement was 18.5 ± 11.4% before surgery and 23.9 ± 14.3% after. For those with no change, it was 29.7 ± 10.8% before and 29.4 ± 9.5% after, and in patients with worsened hearing function it was 22.7 ± 7.5% before and 27.2 ± 13.4% after. Conclusion: We found no correlation between the changes in hearing function and the volume of EH after ELSD.

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Eendolymphatic Hydrops.

OBJECTIVE: To investigate the effects of electroacupuncture (EA) on endolymphatic hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2) pathway in guinea pigs. METHODS: EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala vestibuli (SV) area (R value) was calculated. In mechanical studies, a comparison of plasma AVP (p-AVP) concentrations, cyclic adenosine monophosphate (cAMP) levels, vasopressin type 2 receptor (V2R) and AQP2 mRNA expressions in the cochlea were compared among groups. RESULTS: EA significantly reduced cochlear hydrops in guinea pigs (P=0.001). EA significantly attenuated the AVPinduced up-regulation of p-AVP concentrations (P=0.006), cochlear cAMP levels (P=0.003) and AQP2 mRNA expression (P=0.016), and up-regulated the expression of V2R mRNA (P=0.004) in the cochlea. CONCLUSIONS: The dehydrating effect of EA might be associated with its inhibition of AVP-AQP2 pathway activation.

Effect of electroacupuncture on arginine vasopressin-induced endolymphatic hydrops.

OBJECTIVE: To investigate the influence of electroacupuncture (EA) on experimentally induced endolymphatic hydrops (EH) in guinea pigs, and elucidate the association between the dehydrating effect of EA and changes in stria vascularis ultrastructure and expression of vasopressin type 2 receptor (V2R), cyclic adenosine monophosphate (cAMP), and aquaporin 2 (AQP2) in the endolymphatic sac (ES). METHODS: The EH model was established by intraperitoneal injection of arginine vasopressin (AVP). As a treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once daily for 10 consecutive days. For histomorphological studies, degree of cochlear hydrops was evaluated by hematoxylin-eosin staining, and the ratio of scala media (SM) area to SM + scala vestibuli area was calculated. In mechanical studies, ultrastructural changes in stria vascularis tissue were examined by transmission electron microscopy. In addition, cAMP levels and mRNA expression levels of V2R and AQP2 in the ES were compared among groups. RESULTS: EA treatment significantly reduced cochlear hydrops compared with hydropic guinea pigs (P = 0.015). Furthermore, EA attenuated ultrastructural changes in the stria vascularis tissue following EH, significantly upregulated the expression of V2R (P = 0.016), and attenuated AVP-induced upregulation of both cAMP (P = 0.038) and AQP2 expression (P = 0.017) in the ES. CONCLUSION: Collectively, the results of the present study suggest that the dehydrating effect of EA is associated with improvement of stria vascularis ultrastructure and V2R-cAMP-AQP2 signaling pathway regulation in the ES.

Delayed Effect of Active Pressure Treatment on Endolymphatic Hydrops.

OBJECTIVE: To identify eventual correlations between the effect of low-pressure treatment and endolymphatic hydrops in Ménière patients. MATERIAL AND METHODS: The study group consisted of subjects affected by definite Ménière disease (2015) and a severe degree of disability, who received a ventilation tube with or without a low-pressure treatment before undergoing a surgical procedure (vestibular neurectomy). After the placement of the ventilation tube, the subjects were either left alone with the tube or received 1 month of self-administered low-pressure therapy with a portable device. In all subjects, an electrocochleography (ECochG) was performed and specific questionnaires - Dizziness Handicap Inventory (DHI) and Functional Scale Level (FSL) - were completed before starting either arm of treatment, at the end of treatment, and then 3 and 6 months later. RESULTS: All selected subjects presented with an ECochG pattern that was indicative of endolymphatic hydrops before starting either treatment. At the end of pressure treatment, 80% showed symptomatic improvement while maintaining the hydropic ECochG pattern. At the 3-month control stage, the hydropic pattern resulted normalized (<0.5) in all the improved subjects. CONCLUSIONS: Although 1 month of low-pressure treatment provided a positive symptomatological outcome, normalization of the hydropic ECochG parameters occurred only at a later time. Therefore, it is possible to assume that endolymphatic hydrops could be concurrent with a non-symptomatic stage of Ménière disease, and that the anti-hydropic effect of the low-pressure treatment, if any, would present with a certain delay after its completion.

Endolymphatic hydrops in idiopathic intracranial hypertension: prevalence and clinical outcome after lumbar puncture. Preliminary data.

Idiopathic intracranial hypertension is characterized by raised intracranial pressure (ICP) without any underlying pathology, presenting with (IIH) or without papilledema (IIHWOP). Headache, often on daily basis, is the most frequent symptom. Among audiovestibular symptoms, tinnitus and dizziness are commonly reported, while vertigo and hearing impairment are infrequent reports. Endolymphatic hydrops (ELH) is the typical histopathologic feature of Ménière disease, a condition featured by episodes of vertigo, dizziness, fluctuating hearing loss, tinnitus, and aural fullness. Evidences suggest that ICP is transmitted to inner ear. The aim of this study is to investigate the prevalence of ELH symptoms in IIH/IIHWOP and the relationship between the raised ICP and ELH. The prevalence of chronic headache and of ELH symptoms was investigated in a consecutive series of IIH/IIHWOP patients, and a standard audiometry with hearing threshold measurement (pure-tone average-PTA) was performed. Differences in chronic headache and ELH symptoms prevalence and changes of PTA threshold were calculated after ICP normalization by lumbar puncture (LP). Thirty-one patients (17 with IIH and 14 with IIHWOP) were included. Before LP, chronic headache was present in 93.5%. The percentages of patients reporting tinnitus, dizziness, vertigo, and aural fullness were 67.7, 77.4, 22.6, and 61.3%, respectively. Headache frequency as well as ELH symptoms and PTA significantly improved after LP. The improvement of PTA and of ELH symptoms observed after LP in this series of IIH/IIHWOP patients indicates that a raised ICP, a condition known to be involved in the progression and refractoriness of migraine pain, has also a role in ELH. We propose that intracranial hypertension may represent the shared pathogenetic step explaining the large epidemiological comorbidity between migraine and vestibular symptoms, at present conceptualized as "vestibular migraine."

[Advance in research of delayed endolymphatic hydrops].

Delayed endolymphatic hydrops (DEH) is a disease entity first described by Kamei and named by Schuknecht, defined as profound sensorineural deafness at early stage and after several years started to appear clinical feature of endolymphatic hydrops such as vertigo, aural fullness like Meniere's disease or fluctuating hearing loss in the contralateral ear . DEH can be classified into ipsilateral type, contralateral type and bilateral type. Although DEH has low incident rate, there are many kinds of etiology and audiology and vestibular tests. Up to now, a lot of literatures about etiology, diagnose, clinical manifestation, relevant examination and therapy of DEH were published abroad. In this review, we will make a summary of research status of DEH.

Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation.

HYPOTHESIS: Phosphorus and vitamin D (calcitriol) supplementation in the Phex mouse, a murine model for endolymphatic hydrops (ELH), will improve otic capsule mineralization and secondarily ameliorate the postnatal development of ELH and sensorineural hearing loss (SNHL). BACKGROUND: Male Phex mice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorus and calcitriol. The effect of this treatment has never been studied on otic capsule bone and it is unclear if improving the otic capsule bone could impact the mice's postnatal development of ELH and SNHL. METHODS: Four cohorts were studied: 1) wild-type control, 2) Phex control, 3) Phex prevention, and 4) Phex rescue. The control groups were not given any dietary supplementation. The Phex prevention group was supplemented with phosphorus added to its drinking water and intraperitoneal calcitriol from postnatal day (P) 7-P40. The Phex rescue group was also supplemented with phosphorus and calcium but only from P20 to P40. At P40, all mice underwent auditory brainstem response (ABR) testing, serum analysis, and temporal bone histologic analysis. Primary outcome was otic capsule mineralization. Secondary outcomes were degree of SNHL and presence ELH. RESULTS: Both treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralized did not prevent the development of ELH or SNHL. CONCLUSION: Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.

[Effects of electroacupuncture on cochlea morphology and expression of aquaporins in guinea pigs with endolymphatic hydrops].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on cochlea morphology and expression of aquaporin 1 (AQP1) in guinea pigs with endolymphatic hydrops, so as to explore the possible mechanism of EA on endolymphatic hydrops. METHODS: Forty guinea pigs were randomly divided into a blank group, a model group, a medication group and an EA group, 10 guinea pigs in each one. Model of endolymphatic hydrops was established by using intraperitoneal injection of aldosterone. Guinea pigs in the blank group and model group were treated with identical immobilization as EA group but no treatment was given; guinea pigs in the medication group were treated with intragastric administration of hydrochlorothiazide at a dose of 5 mg/kg, once a day for consecutive 10 days; guinea pigs in the EA group were treated with' EA at "Baihui" (GV 20) and "Tinggong"(SI 19), once a day for consecutive 10 days. The serum ionic concentration in each group was tested by turbidimetric method; hematoxylin-eosin staining was used to measure the severity of cochlea hydrops; immunohistochemical method was used to observe the expression of AQP1 in the cochlea. RESULTS: (1) There was no endolymphatic hydrops in the blank group, moderate-severe endolymphatic hydrops in the model group and slight endolymphatic hydrops in the EA group and medication group. (2) The concentration of K+ and Ca2+ in the EA group was higher than that in the model group and medication group (all P<0. 01); the concentration of Na+ was lower than that in the model group (P< 0. 01) but higher than that in the medication group (P<0. 01); the concentration of Cl- was higher than that in the medication group (P<0. 01), but not significantly different from the model group (P>0. 05). (3) The ratio of expression area of AQP1 in the model group was lower than that in the blank group (P<0. 01); the ratio of expression area of AQP1 in the EA group was higher than that in the model group (P<0. 01), and lower than that in the medication group without significant difference (P>0. 05). CONCLUSION: EA could relieve the endolymphatic hydrops in guinea pigs; the mechanism is likely to be related with up-regulating the expression of AQP1 in cochlea and ion concentration might be an important factor involved.

[Menière's Disease]. / Morbus Menière.

Menière`s disease is one of the most common inner ear and vestibular disorders. It is defined as the idiopathic syndrome of endolymphatic hydrops (ELH). Despite the development of several different animal models of ELH, its etiology and pathogenesis is still unresolved. In humans, endolymphatic hydrops may occur spontaneously or as a consequence of specific disorders with distinct inner ear pathologies, e. g., infectious labyrinthitis, noise induced hearing loss or vestibular schwannoma. Recent imaging studies using MRI have shown that hydropic ear disease is associated not only with the full triad of vertigo, hearing, loss and tinnitus/aural pressure, but also with inner ear symptoms that do not fulfill the clinical criteria of definite Menière's disease as set forth by the AAO-HNS. Therefore, terms like "atypical" or "cochlear"/"vestibular" Menière's disease or "forme fruste" should be avoided and the term "Menière's disease" should universally be applied according only to these guidelines. Besides that, the recent possibility of visualizing endolymphatic hydrops on MRI and thereby ascertaining the diagnosis in difficult cases and new audiovestibular function tests for the indirect detection of endolymphatic hydrops show promising results. Evidenced based reviews of currently available therapeutic options still reveal many uncertainties with regard to efficacy, with the exception of the ablative therapies, e. g., intratympanic gentamicin application.

[Odd stories of patients suffering from Menière's disease]. / Les étranges histoires des patients... et de leurs docteurs (!) dans le tourbillon du Menière!

The cause of Meniere's disease is unknown. The postmortem examination of the temporal bone reveals an "endolymphatic hydrops" of the inner ear. Classically, patients describe episodes of vertigo, fluctuations of hearing and tinnitus. But some report "strange stories" that deserve doctor's attention. This article explains why their history (as those suffering from any other vestibular disorder) is often particular, to recall the few knowledge of the disease, how the endolymphatic hydrops was considered as the cause of the disorder, while it is rather an epiphenomenon, and to show how one can believe, wrongly, that a therapy is efficient after a study that seems however at first correctly performed.