Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere's disease based on three-dimensional real inversion recovery sequence

Abstract Objectives: The degree of endolymphatic hydrops in Meniere's disease may be related to hearing loss. However, the results of prior studies have been inconsistent. We aimed to investigate the relationship between endolymphatic hydrops and hearing loss characteristics in Meniere's disease. Methods: This study included 54 patients (62 ears) with Meniere's disease. Patients underwent three-dimensional real inversion recovery sequences for magnetic resonance imaging and puretone audiometry. Endolymphatic hydrops were assessed according to Gurkov's criteria (2011). Correlations between different degrees of endolymphatic hydrops and pure-tone audiometry, as well as staging, were analysed. Results: Pure tone audiometry and staging were higher for vestibular endolymphatic hydrops complicated by cochlear ones than isolated cochlear or vestibular hydrops (both p<0.05). There was no significant correlation between vestibular endolymphatic hydrops and pure-tonal audiometry or staging (all p > 0.05). The degree of hydrops in the middle turn was correlated with the mid-frequency hearing threshold (p<0.05). The degree of cochlear hydrops was correlated with the audiometry, low-frequency hearing thresholds, mid-frequency hearing thresholds and staging (p<0.01). Conclusion: The types and sites of endolymphatic hydrops based on a 3D-real inversion recovery sequence can be used to indicate the degree of hearing loss in patients with Meniere's disease. Level of evidence: Level III.

cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

Umbrales auditivos en pacientes con enfermedad de Méniere manejados con corticoides transtimpánicos

Introducción: Pese a que el uso de corticoides transtimpánicos en pacientes con enfermedad de Méniere es habitual en muchos centros, la evidencia respecto de su efecto sobre los umbrales auditivos es aún controversial. Objetivo: Estudiar los umbrales auditivos de pacientes con enfermedad de Méniere que recibieron corticoides transtimpánicos en el Servicio de Otorrinolaringología del Hospital Clínico de la Universidad de Chile. Material y Método: Estudio retrospectivo de pacientes con enfermedad de Méniere que consultaron entre los años 2015 y 2021. Se estudiaron los umbrales auditivos, antes y después de 3 inyecciones de dexametasona transtimpánica. Resultados: Se obtuvieron datos completos de 27 pacientes. Al comparar el promedio tonal puro antes y después del tratamiento, no se observaron diferencias significativas. A nivel individual, la variación de cambio de los umbrales auditivos con dexametasona se correlaciona en forma significativa con los umbrales auditivos previos a las inyecciones y con el tiempo transcurrido desde la última inyección, pero no con la edad. Conclusión: La terapia con dexametasona transtimpánica en pacientes con enfermedad de Méniere no altera los umbrales auditivos. Sin embargo, se requieren más estudios, para comprobar, si existe un efecto transitorio en los umbrales auditivos de los primeros días posterior al procedimiento.

Introduction: Although transtympanic corticosteroids are proposed in Méniere's disease patients refractory to standard medical therapy, the evidence regarding the effect of transtympanic corticosteroids on hearing thresholds is still controversial. Aim: To study the hearing thresholds of patients with Méniere's disease who were administrated with transtympanic corticosteroids at the Otorhinolaryngology Service of the University of Chile's Clinical Hospital. Material and Method: Retrospective study of Méniere's disease patients who consulted between 2015 and 2021. Demographic variables and hearing thresholds were studied before and after three transtympanic injections of dexamethasone. Results: A total of 27 patients were studied. There were non-significant differences in pure-tone hearing threshold averages before and after the injections. Individual variation in hearing thresholds correlates significantly with the pre-injection hearing thresholds and the period since the last injection, but not with age. Conclusion: Transtympanic dexamethasone therapy in patients with Meniere's disease does not alter hearing thresholds. However, more studies are needed to verify whether there is a transitory effect on hearing thresholds in the first days after the procedure.

A three-dimensional inversion-recovery with real reconstruction sequence with an ultralong repetition time for endolymphatic hydrops of Meniere disease after intravenous enhancement: a preliminary application / 中华放射学杂志

Objective:To evaluate the value of a three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with an ultralong repetition time (TR) for the endolymphatic hydrops (EH) of Meniere disease (MD) after intravenous gadolinium administration, and compare it with a heavily T 2-weighted three-dimensional fluid-attenuated inversion recovery (hT 2-3D-FLAIR) sequence. Methods:From July 2021 to July 2022, 52 definite MD patients (58 ears) were retrospectively enrolled at Zhongshan Hospital, Fudan University. The 3D-real IR with an ultralong TR (16 000 ms) and hT 2-3D-FLAIR sequences were performed four hours after intravenous single-dose gadolinium administration. The image quality of the two sequences was rated. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured in the two sequence. The EH of cochlear and vestibular was graded, and EH detection rates were calculated. Scores of the two sequences were compared using the paired Wilcoxon signed rank test. Paired t test was used to compare the differences of the SNR and CNR. McNemar test was performed to compare the EH detection rate between the two sequences. Results:The score of the 3D-real IR [3 (3, 4)] was significantly higher than that of the hT 2-3D-FLAIR [2.5 (2, 3), Z=-6.06, P<0.001]. No significant difference was found in SNR of 3D-real IR and hT 2-3D-FLAIR (11.4±6.5 and 12.3±3.7, t=-1.38, P=0.175). CNR of the 3D-real IR (21.7±9.3) was significantly higher than that of the hT 2-3D-FLAIR (9.7±3.8, t=10.67, P<0.001). Using 3D-real IR sequence, the EH detection rate of cochlear (89.7%, 52/58) was higher than using hT 2-3D-FLAIR (67.2%, 39/58, χ 2=11.10, P<0.001). No significant difference was found in the EH detection rate of vestibular between 3D-real IR (77.6%, 45/58) and hT 2-3D-FLAIR (74.1%, 43/58, χ 2=0.50, P=0.500). Conclusion:Compared with hT 2-3D-FLAIR sequence, the 3D-real IR with an ultralong TR can improve the depiction of EH in MD patients after intravenous single-dose gadolinium administration. It can provide higher image quality and detection rate of EH.

The clinical features and image characteristics of Meniere's disease patients with endolymphatic hydrops confirmed by enhanced magnetic resonance imaging

Abstract Objectives: To analyze and summarize the clinical features and image characteristics of Meniere's Disease (MD) patients with Endolymphatic Hydrops (EH) confirmed by enhanced Magnetic Resonance Imaging (MRI). Methods: 252 MD patients with EH confirmed by MRI were enrolled. All patients met the diagnostic criteria forMD and underwent intravenous gadolinium injection. After 4 h, MR examinations were performed. The Nakashima grading standard was used to classify EH and evaluate its correlation with clinical features. Results: Different degrees of EH were shown in all MD patients, and 157 of the 252 (62.3%) patients showed significant EH, 95 of the 252 (37.7%) patients showed mild EH. Only 89 (35.3%) met the diagnostic criteria for definite MD, and the remaining 163 (64.7%) patients met the diagnostic criteria for probable MD. Compared with patients with unilateral EH, the symptoms of the first affected ear of patients with bilateral EH were more serious. The degree of EH was related to the degree of hearing loss (p< 0.05). Conclusion: MRI with intravenous gadolinium injection can provide a better assessment of EH in MD patients. The clinical features of MD patients with EH confirmed by enhanced MRI did not fully meet the existing diagnostic criteria for definite MD. Including the diagnosis of EH in the diagnostic criteria of MD can increase the diagnosis rate of MD. The degree and distribution of EH may be related to the degree of hearing loss. Level of evidence: 4.

Audio-vestibular and radiological analysis in Meniere's disease

Abstract Objective: Intravenous gadolinium-enhanced inner ear magnetic resonance imaging (IV Gd-enhanced inner ear MRI) is a new technique for diagnosing Meniere's disease (MD). Vestibular tests have also long been used forMD, but which tests should be included in the oto-neurological test battery remains controversial. The evaluation method to be used to confirm the clinical diagnosis in MD is not clear. This study aimed to examine the results of vestibular tests and IV Gd-enhanced inner ear MRI in individuals diagnosed with unilateral definite Meniere's disease. Methods: IV Gd-enhanced inner ear MRI (Endolymphatic Hydrops [EH] and Perilymphatic Enhancement [PE]), conventional audiometry (0.25-8kHz), video Head Impulse Test (vHIT), cervical Vestibular Evoked Myogenic Potential (cVEMP), air caloric test, and dizziness handicap inventory were applied to 16 adult patients diagnosed with unilateral definite MD. Results: Among the patients with definite MD, EH (cochlear and/or vestibular) was identified in 93.7% and 68.7% of the symptomatic and the asymptomatic ears, respectively. There was a positive correlation between the hearing thresholds at 2, 4, 6 and 8 kHz and the degree of cochlear EH (p < 0.05). PE (cochlear and/or vestibular) was observed in 37.5% of the asymptomatic and symptomatic ears. The sensitivity of the vestibular test battery (vHIT, cVEMP, and caloric test) was 100% and its specificity was 50%, while the sensitivity of the IV Gd-enhanced inner ear MRI (EH and PE together) was 93.8% and the specificity was 81.3%. Conclusion: MRI had higher sensitivity and specificity than the vestibular test battery. PE or vHIT alone was not considered to be reliable in the diagnosis of MD. In suspected MD, the clinical history, hearing tests, and IV Gd-enhanced inner ear MRI are sufficient for diagnosis. If MRI technique is not possible, vestibular tests (caloric test and cVEMP, not vHIT) can provide reliable results when evaluated together.

Emissões otoacústicas evocadas na doença de Ménière / Otoacoustic emissions evoked in Ménière's disease

RESUMO Objetivo Verificar as respostas das emissões otoacústicas (EOA) evocadas por estímulo transiente e produto de distorção em indivíduos com doença de Ménière. Métodos Estudo transversal com casuística composta por 60 indivíduos de 19 a 75 anos de idade, distribuídos em dois grupos: grupo estudo, com 32 indivíduos com diagnóstico médico de doença de Ménière, sem outros riscos, e grupo controle formado por 28 indivíduos com perda coclear, sem doença de Ménière, pareado por idade e gênero ao grupo estudo. Critério de elegibilidade: curva tipo A, sem perda condutiva ou mista ou suspeita de alteração retrococlear. A avaliação audiológica foi composta por anamnese, inspeção do meato acústico externo, audiometria tonal limiar, logoaudiometria, medidas de imitância acústica e emissões otoacústicas evocadas por estímulo transiente e produto de distorção. Resultados Os indivíduos com Ménière apresentaram maior ocorrência de perda unilateral, zumbido pitch grave, vertigem e plenitude auricular em relação ao controle. Nesses indivíduos, houve maior incompatibilidade entre os resultados das EOA e da audiometria tonal: nas perdas unilaterais, observaram-se alterações nas EOA nas orelhas com limiares auditivos normais do lado contralateral, caracterizando disfunções cocleares. Nas orelhas com perda coclear, houve presença de EOAT (por estímulo transiente) e ausência de EOAPD (produto de distorção), contrapondo-se ao grupo controle, que apresentou ausência de EOAT e de EOAPD, como o esperado em perdas cocleares de outras etiologias. Conclusão A pesquisa das emissões na doença de Ménière identificou disfunção coclear na orelha contralateral nos casos unilaterais e presença de EOAT com ausência de EOAPD nas orelhas com perda auditiva, diferenciando-se das perdas cocleares de outras etiologias.

ABSTRACT Purpose To verify the responses of Evoked Otoacoustic Emissions by transient stimulus and distortion product in individuals with Ménière's Disease. Methods Cross-sectional study with a sample composed of 60 individuals, aged 19 to 75 years, divided into two groups: study group, with 32 individuals with a medical diagnosis of Ménière's disease, without other risks and a control group formed by 28 individuals with cochlear loss without Meniere's disease, age and sex matched to the study group. Eligibility criteria: type A curve, without conductive or mixed loss or suspected retrocochlear alteration. The audiological evaluation consisted of anamnesis, inspection of the external acoustic meatus, pure tone audiometry, logoaudiometry, measures of acoustic immittance and transient evoked otoacoustic emissions and distortion product. Results Individuals with Ménière's disease had a higher occurrence of unilateral hearing loss, low pitch tinnitus, vertigo and ear fullness in relation to the control. In these individuals, there was greater incompatibility between the results of OAE and pure tone audiometry: in unilateral hearing loss, alterations in OAE were observed in ears with normal hearing thresholds on the contralateral side, characterizing cochlear dysfunctions. In the ears with cochlear loss, there was the presence of TEOAE and absence of DPOAE, in contrast to the control group, which showed the absence of TEOAE and DPOAE, as expected in cochlear losses of other etiologies. Conclusion The investigation of emissions in Ménière's disease identified cochlear dysfunction in the contralateral ear in unilateral cases and the presence of TOAE with absence of DPOAE in ears with hearing loss, differentiating from cochlear losses of other etiologies.

Comparative study of quantitative methods based on intravenous enhancement of 3D-FLAIR sequence for evaluation of endolymphatic hydrops / 中华放射学杂志

Objective:To compare the diagnostic value of three quantitative evaluation methods based on three-dimensional rapid fluid attenuation inversion recovery sequence (3D-FLAIR) vein-enhanced labyrinth images in endolymphatic hydrops.Methods:From October 2017 to April 2019, a retrospective study was conducted on 86 patients with unilateral otogenic vertigo who were admitted to Beijing Tongren Hospital, Capital Medical University. MRI was performed 8 h after the single-dose Gd-DTPA intravenously injection in all patients. Three evaluation methods were used to calculate the ratio of the endolymphatic area to the total lymphatic area, the ratio of the saccule to utricle area, and the ratio of the endolymphatic volume to the total lymphatic volume, respectively. The paired t test was used to compare the three ratios between the affected and healthy ears. With clinical diagnosis as the gold standard, the receiver operating characteristic (ROC) curve analysis was used to analyze the efficacy of three methods in diagnosing endolymphatic hydrops. Results:Totally 65 cases were finally diagnosed endolymphatic hydrops clinically. There were statistically significant differences of all the 3 ratios between the affected and healthy ears ( t=9.93, 7.22, 8.20, all P<0.001). The ROC curve showed that the area under the curve (AUC) of endolymph/total lymph area ratio, saccule/utricle area ratio, endolymph/total lymph volume ratio for diagnosis of endolymphatic hydrops were 0.882, 0.768, 0.884 (all P<0.001). And there were no significant differences between each paired AUCs (all P>0.05). Conclusions:All three methods of endolymph/total lymph area ratio, saccule/utricle area ratio, endolymph/total lymph volume ratio can quantitatively evaluate endolymphatic hydrops. The endolymphatic/total lymphatic area ratio method is still the most convenient method at present.

Síndrome de Lermoyez, presentación de caso clínico / Lermoyez´s syndrome, a case report presentation

Lermoyez´ syndrome is an unusual clinical variant of Ménière's disease, because in both pathologies there is a peripheral vascular disorder, what It consists in the dilation of the labyrinthine membranes associated with an increase in the volume of the endolymph. Clinically, they have severe frequency fluctuations of hearing loss, tinnitus and vertigo attacks. FinaIly, it evolves to the deterioration of hearing in all frequencies. Lermoyez´ síndrome, or labyrinthine angiospasm, has an unknown etiopathogeny, although several theories have been proposed, but none explains its nature, nor its clinical course, being one of them the allergy. Their diagnosis is clinical, they present the typical triad (peripheral vertigo crisis with neurosensory hearing loss and tinnitus and/or otic fullness), but they characterised by the improvement in hearing just after a sudden vertigo attack. With the development of the disease, dizziness attacks and hearing recovery become more and more rare, and disappear. Treatment aims to relieve symptoms during crises and improve disease progression. It is present the clinical case of Lermoyez syndrome, in a male patient with allergic pathology, who was diagnosed with Ménière's disease at the beginning. It is a rare syndrome described described in classical ENT (ear-nose-throat)

El síndrome de Lermoyez es una variante clínica inusual de la enfermedad de Ménière. En ambas afecciones existe un trastorno vascular periférico, que consiste en la dilatación de las membranas laberínticas, asociadas con aumento del volumen de la endolinfa. Clínicamente, el individuo presenta fluctuaciones en la audición (hipoacusia neurosensorial en las frecuencias graves), acúfenos y ataques de vértigo. En su evolución final se deteriora la audición en todas las frecuencias. El síndrome de Lermoyez, o angioespasmo laberíntico, tiene una etiopatogenia desconocida, aunque se han propuesto varias teorías, pero ninguna explica su naturaleza ni su curso clínico, y una de ellas es la alergia. Su diagnóstico es clínico, presentan la triada típica (crisis de vértigo periférico con hipoacusia neurosensorial y acúfenos o plenitud ótica), pero el síndrome de Lermoyez se caracteriza por la mejora de la audición tras un ataque brusco de vértigo. Con el avance de la enfermedad, los ataques de vértigo y la recuperación de la audición llegan a ser cada vez más raros, hasta desaparecer. El tratamiento tiene como finalidad aliviar los síntomas durante las crisis y mejorar la evolución de la enfermedad. Se presenta un caso clínico de síndrome de Lermoyez, en un paciente varón con afección alérgica, cuyo diagnóstico de inicio fue de enfermedad de Ménière. Es un síndrome infrecuente, descrito en la otorrinolaringología clásica

Resonancia magnética en enfermedad de Ménière

Resumen La enfermedad de Ménière (EM) es una conocida causa de vértigo crónico asociado a múltiples síntomas audiológicos fluctuantes (hipoacusia, tinnitus, plenitud aural). Su fisiopatología no es completamente comprendida, pero se ha relacionado al hidrops endolinfático (HE) como entidad principal. A la fecha, varios estudios electrofisiológicos han intentado posicionarse como pruebas diagnósticas definitivas, pero no lo han logrado, ya sea por dificultad técnica para realizarlos o por resultados inconsistentes en la literatura internacional. Pero cabe destacar que varios hallazgos son altamente sugerentes de enfermedad de Ménière como la presencia de una baja tasa de respuesta asociado al aumento del umbral de esta misma en los VEMPs (vestibular evoked myogenic potentials), tanto oculares como cervicales, o el aumento del cuociente entre el potencial de sumación/potencial de acción en la electrococleografía. A pesar de estas pruebas, hasta el día de hoy, el diagnóstico se sigue realizando en base a criterios clínicos consensuados internacionalmente, dado lo dificultosa que es la visualización directa del HE y falta de compresión de otros mecanismos fisiopatológicos de esta enfermedad. En las últimas décadas, ha habido avances prometedores en la detección de hidrops endolinfático con el uso de resonancia magnética, permitiendo la visualización de los espacios peri y endolinfáticos usando gadolinio como contraste. A su vez, esto ha permitido mejoría de las secuencias imagenológicas usadas, el desarrollo de varias nuevas técnicas de procesamiento de imágenes, conllevando que varias escalas o clasificaciones de HE hayan sido propuestas, las cuales serán revisadas en detalle en este trabajo.

Abstract Ménière's disease (MD) is a known cause of chronic vertigo, with multiple fluctuating audiological symptoms (hearing loss, tinnitus, aural fullness). The pathophysiology is not completely understood but has been attributed to endolymphatic hydrops (EH). There are many electrophysiological tests available, but none of them can be considered as the gold standard, either because of difficult technique or inconsistent results in the literature. Nonetheless, some findings are highly suggestive of MD, like the presence of a low response and high threshold in ocular and cervical VEMPs (vestibular evoked myogenic potentials), or the increased ratio between the amplitudes of summation potential and action potential in the electrocochleography. Despite the availability of these tests, the diagnosis of MD is still made clinically, following the diagnostic criteria establish by international consensus, due to the difficulty to visualize the EH and also the lack of full comprehension of other pathophysiological mechanisms. In the last decades, there have been promising advances in the detection of endolymphatic hydrops with magnetic resonance imaging, allowing the visualization of the perilymphatic and endolymphatic space using gadolinium as a contrast agent. At the same time, the imaging sequences have improved, new techniques for imaging processing have been developed, entailing that various classifications or graduation systems for EH have been proposed, which will be review in detail, in this paper.

Gadolinium-enhanced MRI reveals dynamic development of endolymphatic hydrops in Ménières disease / Ressonância magnética com gadolínio revela o desenvolvimento dinâmico da hidropsia endolinfática na doença de Ménière

Abstract Introduction: Meniere's disease is associated with impaired hearing, tinnitus, vertigo, and aural fullness. Many anatomical studies have suggested idiopathic endolymphatic hydrops as the pathological basis of Meniere's disease, which now can be visualized by using gadolinium -enhanced magnetic resonance imaging of the inner ear. Objective: To investigate the development of endolymphatic hydrops in Meniere's disease by monitoring the vestibules and cochleae of affected patients. Methods: Inner ears of 178 patients with definite unilateral Meniere's disease diagnosis were visualized by 3-dimensional fluid-attenuated inversion recovery and three-dimensional real inversion recovery magnetic resonance imaging following bilateral gadolinium intratympanic injection. The scans were used to evaluate the presence and degree of endolymphatic hydrops in the vestibules and cochlear structures, including the cochlear apical turn, the cochlear middle turn, and the cochlear basal turn. The correlation of endolymphatic hydrops occurrence between the various parts of the inner ear was determined. Results: Symptomatic endolymphatic hydrops was detected on the affected side in all patients, whereas asymptomatic endolymphatic hydrops was detected on the unaffected contra-lateral side in 32 patients (18.0%). On the affected side, the cochlear apical turn and the cochlear middle turn demonstrated significantly higher rates of endolymphatic hydrops than the cochlear basal turn and the vestibule. The severity of endolymphatic hydrops gradually decreased from the cochlear apical turn to the cochlear basal turn. On the contra lateral side, the incidence and degree of the detected asymptomatic endolymphatic hydrops were significantly greater in the cochleae than in the vestibules (p < 0.05), with no significant difference detected between the cochlear turns. Conclusion: Progression of endolymphatic hydrops appears to be directional, initiated in the cochlea. The order of endolymphatic hydrops severity gradually decreases from the cochlear apical turn to the cochlear basal turn and then to the vestibule. Endolymphatic hydrops in the vestibule is associated with symptomatic Meniere's disease.

Resumo Introdução: A doença de Ménière está associada a deficiência auditiva, zumbido, vertigem e plenitude auricular. Muitos estudos anatômicos sugerem hidropsia endolinfática idiopática como a base patológica da doença, que agora pode ser visualizada através de estudo por imagem da orelha interna por ressonância magnética com gadolínio. Objetivo: Investigar o desenvolvimento da hidropsia endolinfática na doença de Ménière com monitoramento dos vestíbulos e das cócleas dos pacientes afetados. Métodos: Orelhas internas de 178 pacientes com diagnóstico definitivo de doença de Ménière unilateral foram visualizados através de imagem de recuperação de inversão atenuada por fluidos em ressonância magnética tridimensional, 3-D FLAIR, e por inversão real após injeção intratimpânica bilateral de gadolínio. Os exames foram usados para avaliar a presença e o grau de hidropsia endolinfática nos vestíbulos e nas estruturas cocleares, inclusive o giro coclear apical, o giro coclear médio e o giro coclear basal. A correlação da ocorrência de hidropsia endolinfática entre as várias partes da orelha interna foi determinada. Resultados: Hidropsia endolinfática sintomática foi detectada no lado afetado em todos os pacientes, enquanto hidropsia endolinfática assintomática foi detectada no lado contralateral não afetado em 32 pacientes (18,0%). No lado afetado, o giro apical da cóclea e o giro coclear médio demonstraram taxas significativamente mais altas de hidropsia endolinfática do que o giro basal e o vestíbulo. A gravidade da hidropsia endolinfática diminuiu gradualmente do giro apical da cóclea para o giro basal. No lado contralateral, a incidência e o grau da hidropsia endolinfática assintomática detectada foram significantemente maiores nas cócleas do que nos vestíbulos (p < 0,05), sem diferença significante entre os giros cocleares. Conclusões: A progressão da hidropsia endolinfática parece ser direcional, iniciando-se na cóclea. A sua ordem da gravidade diminui gradualmente do giro apical da cóclea para o giro basal e, em seguida, para o vestíbulo. A hidropsia endolinfática no vestíbulo está associada à doença de Ménière sintomática.

Trans-tympanum and intravenous administration of contrast agents 3D-FLAIR MR inner ear imaging in patients with Meniere's disease / 中国医学影像技术

Objective: To observe the changes of inner ear in patients with Meniere's disease with 3D-FLAIR MRI after intratympanic (IT) gadolinium injection or intravenous (IV) gadolinium injection. Methods: Totally 36 patients with Meniere's disease were randomly divided into 2 groups. Eighteen of them underwent intravenous injection of GD-BOPTA (IV group), while the rest 18 underwent bilateral IT injection of equivalent dilution of GD-DTPA (IT group). 3D-FLAIR MR examinations were performed after 4 and 24 hours, respectively. ROIs in cochlear perilymph and medulla oblongata were drawn on MRI, and signal-intensity ratio (CM ratio) was subsequently evaluated and compared with paired t test. In addition, the ratio of endolymphatic hydrops (EH) of each group were separately observed and analyzed using chi-squared test. Results: For IT group, comparable CM ratios were found between the affected and unaffected sides of perilymph regions (1.86±0.74 vs 1.68±0.77,n=18,P=0.805). For IV group, significant difference of CM ratios was observed between the affected and unaffected sides of perilymph regions (1.46±0.31 vs 1.26±0.21, n=18, P=0.001). Meanwhile, significantly higher CM ratio was shown in affected sides of perilymph in IT group than that in IV group (1.86±0.74 vs 1.46±0.31,n=18, P=0.044), and significantly higher CM ratio was found in unaffected sides of perilymph in IT group than that in IV group (1.68±0.77 vs 1.26±0.21, n=18, P=0.032). Conclusion: Trans-tympanum administration and intravenous administration inner ear MRI show the same effect, and the former has higher signal intensity, while bilateral inner ear and blood-labyrinth barrier permeability could be observed using the latter with less injury.

Uso de gentamicina transtimpánica: experiencia del Hospital Clínico de la Universidad de Chile / Transtympanic gentamicin: experience in Hospital Clínico Universidad de Chile

RESUMEN Introducción: La gentamicina transtimpánica se utiliza en el manejo de pacientes con vértigo crónico refractario al manejo médico. Objetivo: Describir y analizar las características clínicas, epidemiológicas, y resultados de pacientes sometidos a tratamiento con gentamicina transtimpánica en el Hospital Clínico de la Universidad de Chile. Material y método: Estudio retrospectivo, descriptivo, incluyendo los pacientes con patología otorrinolaringológica que hayan recibido gentamicina transtimpánica entre los años 2008 y 2018. Se analizaron variables epidemiológicas, clínicas, y función vestibular. Resultados: La serie está constituida por diez pacientes, con una edad promedio de 52,4 años; siete mujeres y tres hombres. El diagnóstico fue en su mayoría enfermedad de Ménière (7 pacientes). El número promedio de inyecciones de gentamicina fue de 2,8. En el período de seguimiento (rango 1-96 meses), se logró mejoría del vértigo en la mayoría de los pacientes (8 de 10). Conclusión: El tratamiento con inyecciones de gentamicina transtimpánica es una opción importante para aliviar la sintomatología de pacientes con vértigo crónico intratable. Debe indicarse en casos seleccionados, y siempre realizar un estudio auditivo y vestibular completo antes y después del tratamiento con gentamicina.

ABSTRACT Introduction: Transtympanic gentamicin is used for treatment of patients with chronic vertigo refractory to medical management. Aim: To describe and analyze the clinical outcome of patients whom underwent treatment with transtympanic gentamicin at the Clinical Hospital Universidad de Chile. Material and method: Retrospective and descriptive study including patients with otolaryngologist disease whom underwent treatment with transtympanic gentamicin between 2008 and 2018. Epidemiological, clinical variables and vestibular function were analyzed. Results: The serie consists of ten patients, 7 men and 3 women, with an average age of 52,4 years. The most frequent diagnosis was Ménière disease (7 patients). The average number of gentamicin injections was 2,8. The follow up varies from 1 to 96 months, presenting improvement of vertigo in the majority of the cases (8 of 10 patients). Conclusion: The treatment with transtympanic injections of gentamicin is a relevant option to decrease symptoms in patients with chronic intractable vertigo. It should be indicated in selected patients. Prior and posterior the treatment, patients must be studied with a complete evaluation of the auditory and vestibular function.

Menière's disease and disorders of the carbohydrate metabolism involving the inner ear

Introduction: Menière's disease was described in 1861, but there are still uncertainties regarding its pathophysiology and treatment. Endolymphatic hydrops is recognized as a fundamental pathological characteristic of the disease, as a result of an inadequate absorption of the endolymph. A milder type of endolymphatic hydrops results from an altered chemical composition of the endolymph, due to disorders of the carbohydrate metabolism. Objective: To describe the association of both types of hydrops in patients with Menière disease. Methods: This was a retrospective study of 98 patients with Menière's disease, 62 of whom also presented disorders of the carbohydrate metabolism, and 5 patients with delayed endolymphatic hydrops, 2 of whom also presented disorders of the carbohydrate metabolism. Results: The follow-up of these patients showed that the correction of the metabolic disorders may help in the clinical treatment of Menière's disease and of delayed endolymphatic hydrops, but this does not happen in the more severe types of the diseases. Conclusion: Patients with Menière's disease may present simultaneous disorders of the carbohydratemetabolism, affecting the inner ear. The correction of these disorders helps the clinical treatment but does not preclude the progression of the more severe cases of Menière disease (AU)

The role of magnetic resonance imaging in Ménière disease: the current state of endolymphatic hydrops evaluation / O papel da ressonância magnética na doença de Ménière: a avaliação da hidropsia endolinfática nos dias atuais

ABSTRACT Technical advances in magnetic resonance imaging have allowed to accurately detect and grade endolymphatic space distension in Ménière disease; this was only possible in post-mortem histological studies until a few years ago. Magnetic resonance imaging rules out other causes of vertigo and hearing loss, and is able to evaluate the cochlear and vestibular compartments of the endolymphatic space using a dedicated protocol.

RESUMO Os avanços técnicos na ressonância magnética têm permitido detectar e classificar com acurácia a distensão do espaço endolinfático na doença de Ménière; isso só era possível nos estudos histológicos post-mortem até poucos anos atrás. Além de afastar outras causas de vertigem e de perda auditiva, a ressonância magnética é capaz de avaliar os compartimentos coclear e vestibular do espaço endolinfático por meio de um protocolo dedicado.

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Eendolymphatic Hydrops / 中国结合医学杂志

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.

Suspensory Tethers and Critical Point Membrane Displacement in Endolymphatic Hydrops

Abstract Introduction Grossly displaced membranes are characteristic of endolymphatic hydrops. The process whereby physiological membrane displacement becomes pathological may be mediated by stress, but the membrane biomechanics underlying this transition are unclear. Objective This study seeks to determine the role of suspensory tethers during pressure-induced membrane displacement in the generation of the membranous lesions seen in this disease entity using a biomechanical model approach. Methods The location of membrane suspensory tethers was identified histologically. The influence of tethers on model membrane configuration during displacement was assessed graphically. The relationship of membrane configuration during displacement to curvature radius was quantified trigonometrically. The relationship of curvature radius to stress susceptibility was determined mathematically. The net effect of suspensory tethers on membrane stress levels for various degrees of membrane distention and displacement was then calculated numerically. Results In the inferior labyrinth, suspensory tethers are found to occur on the membranes' boundaries. Such tethering is found to impose a biphasic effect on membrane curvature with increasing degrees of displacement. As a consequence, tensile stress susceptibility is found to decline with initial membrane displacement to a critical point nadir beyond which stress then increases monotonically. No such effect was found for the superior labyrinth. Conclusion Boundary tethers in the inferior labyrinth are associated with significant tensile stress reductions until a critical point of membrane displacement is reached. Displacements short of the critical pointmay be physiological and even reversible,whereas such displacements beyond the critical point are apt to be overtly hydropic and irreversible.

Optimization of delivering minimum Gd-DTPA at the posterior upper point on tympanic medial wall and hT2W-3D-FLAIR sequence for detecting endolymphatic hydrops / 中华耳鼻咽喉头颈外科杂志

Objective@#To optimize delivery of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA) at the posterior upper point on tympanic medial wall and heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery (hT2W-3D-FLAIR) sequence, and to implement the technique of detecting endolymphatic hydrops using gadolinium-enhancement MRI.@*Methods@#Thirteen patients with periphery vertigo, who visited Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Changhai Hospital during June and December of 2017, were enrolled in the study.0.10-0.20 ml of Gd-DTPA in various dilutions (10, 20, and 40-fold) were delivered at the posterior upper point on tympanic medial wall using a soft-tipped tympanic suction and drug-spraying needle through an artificially perforated tympanic membrane. Inner ear MRI was performed at 8, 24 h after Gd-DTPA administration using a 3T MR machine in combination with a 20-channel Tim 4G head/neck coil and the sequence of hT2W-3D-FLAIR to detect the gadolinium-enhancement signal within the inner ear and possible endolymphatic hydrops. The scanning time was either 8 min 35 s or 15 min 11 s.@*Results@#Efficient inner ear uptake of Gd-DTPA was detected and induced high signal to noise ratio of MRI in patients receiving targeted delivery of 0.15-0.20 ml of 10-fold diluted contrast agent at the posterior upper point on tympanic medial wall. At 8 h after delivery, significant uptake was detected in the scala tympani and vestibuli of hook region and basal turn of the cochlea, and perilymhatic compartment of the vestibule. At 24 h after delivery, the distribution of Gd-DTPA became homogenous in each turn of the cochlea and perilymphatic compartment of the vestibule. However, obvious individual variance existed in the inner ear uptake when 0.10 ml of 40-fold diluted Gd-DTPA was delivered. Efficient inner ear uptake and high quality images that generated in patients receiving 0.10, 0.15, and 0.20 ml of 20-fold Gd-DTPA demonstrated endolymphatic hydrops with minor individual variance. There was insignificant difference in the enhancement signal of inner ear between 0.15 and 0.10 ml groups when Gd-DTPA was diluted at 20-fold except for the signal of semicircular canal of 0.15 ml group (190.00±53.95 vs 165.50±42.13, t=2.61, P<0.05). There was insignificant difference in the image quality between 8 min 35 s and 15 min 11 s canning time. Various degrees of endolymphatic hydrops were detected in 7 cochleae and 11 vestibule, and both simultaneous cochlear and vestibular endolymphatic hydrops were detected in 4 ears. Cochlear endolymphatic hydrops was detected in all the 3 patients with definite Meniere′s disease, and 2 of them had combined cochlear and vestibular endolymphatic hydrops. Endolymphatic hydrops was not detected in patients with possible Meniere′s disease nor with symptoms of superior semicircular canal dehiscence.@*Conclusion@#Targeted delivery of 0.10 ml with 20-fold diluted Gd-DTPA (total dosage of 5 μmol) at the posterior upper point on tympanic medial wall in combination with 8 min 35 s scanning time hT2W-3D-FLAIR sequence for inner ear MRI in a 3T MR machine is a clinically practical method to detect endolymphatic hydrops, and reduce the requirement for MRI hardware.

Recent Research Trend for Ménière's Disease / 대한평형의학회지

Ménière's disease is a poorly understood disorder of the inner ear characterized by intermittent episodic vertigo, fluctuating hearing loss, ear fullness and tinnitus. In this paper, we present a review of the histopathology, cytochemistry, gene, blood-labyrinthine barrier and imaging of Ménière's disease. Histopathology is significant for neuroepithelial damage with hair cell loss, basement membrane thickening, perivascular damage and microvascular damage. Cytochemical alterations are significant for altered AQP4 and AQP6 expression in the supporting cell, and altered cochlin and mitochondrial protein expression. Since the discovery of aquaporin water channels (AQP1, AQP2, AQP3, AQP4, AQP5, AQP6, AQP7 and AQP9), it has become clear that these channels play a crucial role in inner ear fluid homeostasis. Several gene studies related to Ménière's disease have been published, but there is no clear evidence that Ménière's disease is associated with a special gene. Currently, imaging techniques to determine the extent and presence of endolymphatic hydrops are being studied, and further studies are needed to correlate the visualization of the endolymphatic hydrops with clinical symptoms.

Ménière's Disease and Electrophysiology / 대한평형의학회지

Inner ear is composed of cochlea, vestibule, and endolymphatic sac which are enclosed by thin layer of epithelial cells. The enclosed space is filled with fluid named as endolymph where the [K⁺] is high and [Na⁺] is low. This unique ion composition is very important in maintaining normal hearing and balance function by providing K⁺ ions into sensory hair cells, which finally depolarize hair cells to facilitate the transport of sound and acceleration stimulation to central nervous system. The ion composition of inner ear is maintained by various ion transport through ion channels, transporters, and exchangers in the inner ear sensory and extra-sensory epithelium. The disruption of normal endolymphatic ion composition by the deterioration of the function of those ion channels can cause dysfunction of sensory epithelium, which consequently results in hearing and balance disorders. One of the possible pathology from the disruption of inner ear ion homeostasis is endolymphatic hydrops which is a phenomenon of excessive fluid accumulation of inner ear. The dysfunction of ion channels in inner ear epithelium can be an etiology of Ménière's disease since endolymphatic hydrops is a main pathological finding of the disease. In this review, we discussed about the possible pathological mechanism of Ménière's disease as a perspective of channelopathy as well as the role of various ion channels in the regulation of inner ear fluid volume based on the findings revealed by electrophysiological studies.