Endolymphatic Sac Research Articles

Comparison of the Pathway to the Inner Ear Between Postauricular and Intramuscular Injection of Dexamethasone in Guinea Pigs

BackgroundPostauricular injection as a local therapy has been confirmed to be effective for inner ear diseases. However, the mechanism for the drugs entering the inner ears remains unknown. This study aims to compare the distribution of dexamethasone by intramuscular injection with that by postauricular injection, and explore the pathway of the drugs entering the inner ears.MethodsAn in vivo optical imaging system was used to conduct a time course observation to compare the distribution of dexamethasone by intramuscular injection with that by postauricular injection in male guinea pigs. The drug availability in the tympanic mucosa, tympanum, endolymphatic sac, and cochlea was observed by a confocal laser scanning microscope.ResultsThe local fluorescent intensity by postauricular injection was significantly higher in the inner ears, and lower in partial peripheral organs, than that by the intramuscular injection. The drug metabolism by postauricular injection exhibited an obviously sustained release effect in the inner ears. Drugs by postauricular injection might enter the endolymphatic sac through the posterior auricular artery and occipital artery, as well as the connections of the mastoid emissary vein, sigmoid sinus and endolymphatic sac.ConclusionMore drugs concentrated in the inner ear for longer therapeutic time and less systemic delivery implied more effective and less risk of side effects through postauricular injection than intramuscular injection safer for the treatment of inner ear diseases.

Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Familial Tumor Syndromes.

The initiative of the 5th edition of the WHO classification of the Head and Neck Tumours establishing a new section dedicated to familial/heritable tumor syndromes with tumors and lesions in the head and neck region was much needed to better understand the tumours, diseases, and associated syndromes, as well as establish recommendations for monitoring and treating these patients. (WHO Classification of Tumours Editorial Board. Head and Neck tumours. Lyon (France): International Agency for Research on Cancer; 2022. https://publications.iarc.fr/ ). Within the newly established chapter on genetic tumor syndromes, we have described the main manifestations on the head and neck region in 15 syndromes. This review highlights the important findings within these syndromes, especially on the update on syndromes with tumors involving the head and neck region, as Gorlin syndrome/nevoid basal cell carcinoma syndrome associated with odontogenic keratocysts; Brooke-Spiegler syndrome/familial cylindromatosis and the associated membranous-type salivary gland basal cell adenoma, PTEN hamartoma tumor syndrome/Cowden syndrome with associated facial skin and mucosal lesions and characteristic multinodular thyroid lesions, Von Hippel Lindau syndrome and the associated middle ear endolymphatic sac tumor, as well as the fascinating genetic aspects of the diverse Head and Neck Paragangliomas. We will also discuss hyperparathyroidism-jaw tumor syndrome is characterized by parathyroid tumors in association with fibro-osseous jaw tumors, as well as head and neck desmoid tumors associated with familial adenomatous polyposis with Gardner syndrome variant familial, multicentric head and neck squamous cell carcinoma, tuberous sclerosis and neurofibromatosis type 1-associated head and neck lesions.

Comparative analysis of the effectiveness of the alternatives current treatments in Meniere’s disease

<p class="abstract">The objective is to compare the efficacy of the treatments currently used in Ménière's disease, assessing their advantages and disadvantages. A bibliographic review was carried out with 11 original articles, of which 10 are in English and 1 in Spanish, from 3 years to date in Journal of Vestibular Research, Otology & Neurotology, European Archives Oto-Rhino-Laryngology, American Journal of Otolaryngology, Laryngoscope Investigative Otolaryngology, Journal of Neurology, Iranian Journal of Otorhinolaryngology, Revista Ciencia y Salud, respectively. The following books were consulted Harrison's Principles of Internal Medicine; Oído, nariz, garganta y cirugía de cabeza y cuello; Diagnóstico y tratamiento en otorrinolaringología. Cirugía de cabeza y cuello; and, Tratado de otorrinolaringología y patología cervicofacial. Medical treatment with dexamethasone, gentamicin, betahistine and diuretics was evaluated, as well as surgical treatment with endolymphatic sac surgery, vestibular neurectomy and labyrinthectomy. Treatment is individualized, however, betahistine is recommended as the first option, followed by IT gentamicin for the control of vertigo.</p>

Up-Regulated Expression of Interferon-Gamma, Interleukin-6 and Tumor Necrosis Factor-Alpha in the Endolymphatic Sac of Meniere's Disease Suggesting the Local Inflammatory Response Underlies the Mechanism of This Disease.

BackgroundImmune mediated inflammatory changes affecting the endolymphatic sac (ES) may underlie the pathology of Meniere's disease (MD). The aim of the present study was to explore the differentially expressed cytokines in ES luminal fluid (ELF) of patients with MD, and the correlation between the expression of cytokines in the ELF with that in the serum was determined by quantitatively analyzing the cytokines in human ELF and serum.MethodsHuman ELF, serum and ES tissues were collected from patients with unilateral MD and patients with acoustic neuroma (AN) during surgery. The Simoa Cytokine 6-Plex Panel kit was used to analyze the levels of cytokines in the ELF and blood samples of the patients. Immunohistochemistry and immunofluorescence were subsequently used to validate the relative expression levels of the cytokines in MD.ResultsSignificant differences were identified in the expression levels of interferon-γ (IFN-γ) (P < 0.001), interleukin (IL)-6 (P = 0.008) and tumor necrosis factor-α (TNF-α) (P = 0.036) in the luminal fluid of the ES comparing between the MD and AN groups. By contrast, the levels of IFN-γ, IL-10, IL-12p70, IL-17A, IL-6 and TNF-α in the serum of the MD group were not significantly different from those of either the AN group or healthy control subjects. In addition, no significant correlations in the expression levels of cytokines compared between the ELF and serum were found for the patients in either the MD or the AN group. Finally, the detection of positive expression of TNF-α, IL-6 and IFN-γ in the epithelial cells of the majority of ES specimens from patients with MD confirmed the up-regulated expression of these cytokines in the ES of patients with MD.ConclusionsThe identification of up-regulated expression levels of TNF-α, IL-6 and IFN-γ in the ELF in the present study has provided direct evidence for an increased immunologic activity in the microenvironment of the ES in patients with unilateral MD, may suggest the local inflammatory response underlies the mechanism of this disease.

Immunohistochemical expression of carbonic anhydrase 9, glucose transporter 1, and paired box 8 in von Hippel-Lindau disease–related lesions

von Hippel-Lindau (VHL) disease occurs secondary to pathogenic alterations of the VHL tumor suppressor gene, manifesting with cysts and tumors in multiple organ systems. VHL protein (pVHL) is a known downregulator of hypoxia inducible factor-1a (HIF1a). Loss of function of pVHL is associated with upregulation of the HIF1a pathway including carbonic anhydrase 9 (CA9)and glucose transporter 1 (GLUT1). Paired box 8 (PAX8) is an important transcription factor regulator of mesonephric development. We investigated the role of immunohistochemistry in the assessment of CA9, GLUT1, and PAX8 expression in VHL disease-related lesions. Clinicopathologic information and archived pathology material from 5 patients with VHL disease were reviewed and evaluated for expression ofCA9, GLUT1, and PAX8. The spectrum of VHL disease-related lesions includedhemangioblastoma, endolymphatic sac tumor, pulmonary microcysts, pheochromocytoma, pancreatic neuroendocrine tumor and serous cystadenoma, renal cysts, renal cell carcinoma, and epididymal papillary cystadenoma. CA9 was expressed in all lesions and exhibited diffuse positivity (15/15 lesions, 100%; 5/5 patients), while GLUT1 expression was focal/weak or absent in some instances (strong positive: 12/15 lesions, 80%; 5/5 patients). PAX8 was expressed only in renal and epididymal lesions. CA9 and GLUT1 are consistently overexpressed in VHL disease-related lesions, reflecting upregulation of the HIF1a pathway. PAX8 is only expressed in genitourinary lesions, mirroring organ-specific differentiation. A combination of CA9 and GLUT1 immunostains is useful in screening lesions of patients with VHL spectrum manifestations, which may be targeted by the recently Food and Drug Administration-approved HIF-2a inhibitors.

A Comparison of Local Endolymphatic Sac Decompression, Endolymphatic Mastoid Shunt, and Wide Endolymphatic Sac Decompression in the Treatment of Intractable Meniere's Disease: A Short-Term Follow-Up Investigation.

BackgroundMeniere's disease (MD) is an inner ear disorder, characterized by recurrent attacks of vertigo, low-frequency sensorineural hearing loss, tinnitus, and aural fullness. Endolymphatic sac surgery is an effective treatment to control vertigo attacks but without causing a hearing loss for intractable MD. However, the methods and effects of endolymphatic sac surgery have been controversial for many years, and the relationship between the vertigo control rates of different endolymphatic sac surgery methods is not well-documented.ObjectivesThis study compared the vertigo control rate, hearing outcome, and quality of life (QOL) among different endolymphatic sac surgery, such as local endolymphatic sac decompression (LESD), endolymphatic sac mastoid shunt (ESMS), and wide endolymphatic sac decompression (WESD).Materials and MethodsWe retrospectively analyzed the patients who underwent endolymphatic sac surgery from January 2008 to June 2019. The control rate of vertigo and QOL scores were compared after 2 years of follow-up. The QOL was scored with validation of the MD patient-oriented symptom-severity index (MDPOSI). The pure tone thresholds of all patients at pre- and postoperation were also compared.ResultsIn total, 83 MD patients with complete follow-up data were included in the study, i.e., 20 patients with LESD, 28 patients with ESMS, and 35 patients with WESD. Results showed a better vertigo control with WESD than the other groups (70% with LESD, 71.4% with ESMS, and 88.6% with WESD). The QOL was improved after surgery in all groups in which the difference was statistically significant (QOL, preoperative vs. postoperative, 38.2 vs. 10.1 with LESD, 37.8 vs. 9.6 with ESMS, and 37.6 vs. 8.3 with WESD), respectively. After endolymphatic sac surgery, the hearing was well-preserved in the three groups [pure tone averages (PTAs), dB, preoperative vs. postoperative, 41.0 ± 19.3 vs. 40.8 ± 17.9 with LESD, 39.7 ± 16.4 vs. 40.8 ± 18.2 with ESMS, and 38.5 ± 18.7 vs. 36.6 ± 19.5 with WESD].ConclusionWide endolymphatic sac decompression has a higher vertigo control rate, better improvement of QOL, and relatively higher hearing stability or improvement rate after surgery in patients with MD compared with LESD and ESMS.

Low-salt diet increases mRNA expression of aldosterone-regulated transporters in the intermediate portion of the endolymphatic sac.

The endolymphatic sac is a small sac-shaped organ at the end of the membranous labyrinth of the inner ear. The endolymphatic sac absorbs the endolymph, in which the ion balance is crucial for inner ear homeostasis. Of the three sections of the endolymphatic sac, the intermediate portion is the center of endolymph absorption, particularly sodium transport, and is thought to be regulated by aldosterone. Disorders of the endolymphatic sac may cause an excess of endolymph (endolymphatic hydrops), a histological observation in Meniere's disease. A low-salt diet is an effective treatment for Meniere's disease, and is based on the assumption that the absorption of endolymph in the endolymphatic sac abates endolymphatic hydrops through a physiological increase in aldosterone level. However, the molecular basis of endolymph absorption in each portion of the endolymphatic sac is largely unknown because of difficulties in gene expression analysis, resulting from its small size and intricate structure. The present study combined reverse transcription-quantitative polymerase chain reaction and laser capture microdissection techniques to analyze the difference of gene expression of the aldosterone-controlled epithelial Na+ channel, thiazide-sensitive Na+-Cl- cotransporter, and Na+, K+-ATPase genes in the three individual portions of the endolymphatic sac in a rat model. A low-salt diet increased the expression of aldosterone-controlled ion transporters, particularly in the intermediate portion of the endolymphatic sac. Our findings will contribute to the understanding of the physiological function of the endolymphatic sac and the pathophysiology of Meniere's disease.

Posterior petrous face meningiomas presenting with Ménière's-like syndrome: a case series and review of the literature.

Ménière's disease is an inner ear disorder classically characterized by fluctuating hearing loss, tinnitus, and aural fullness accompanied by episodic vertigo. While the pathogenesis of Ménière's remains under debate, histopathological analyses implicate endolymphatic sac dysfunction with inner ear fluid homeostatic dysregulation. Little is known about whether external impingement of the endolymphatic sac by tumors may present with Ménière's-like symptoms. The authors present a case series of 7 patients with posterior fossa meningiomas that involved the endolymphatic sac and new onset of Ménière's-like symptoms and review the literature on this rare clinical entity. A retrospective review of patients undergoing resection of a posterior petrous meningioma was performed at the authors' institution. Inclusion criteria were age older than 18 years; patients presenting with Ménière's-like symptoms, including episodic vertigo, aural fullness, tinnitus, and/or hearing loss; and tumor location overlying the endolymphatic sac. There were 7 cases of posterior petrous face meningiomas involving the vestibular aperture presenting with Ménière's-like symptoms. Imaging and intraoperative examination confirmed no cranial nerve VIII compression or labyrinthine artery involvement accounting for audiovestibular symptoms. Of the 7 patients in the series, 6 experienced significant improvement or resolution of their vertigo, and all 7 had improvement or resolution of their tinnitus after resection. Of the 5 patients who had preoperative hearing loss, 2 experienced improvement or resolution of their ipsilateral preoperative hearing deficit, whereas the other 3 had unchanged hearing loss compared to preoperative evaluation. Petrous face meningiomas overlying the endolymphatic sac can present with a Ménière's syndrome. Early recognition and microsurgical excision of these tumors is critical for resolution of most symptoms and stabilization of hearing loss.

Imaging Analysis of Patients With Meniere's Disease Treated With Endolymphatic Sac-Mastoid Shunt Surgery.

Objective: Endolymphatic sac surgery is effective in treating intractable Meniere's disease (MD), but the underlying mechanism is still unknown. Our study investigated the mechanism by which endolymphatic sac-mastoid shunt (EMS) surgery is effective in treating MD by means of imaging.Methods: The experiment included 19 patients with intractable MD who underwent 3D-fluid-attenuated inversion recovery (FLAIR) MRI with a 3-Tesla unit 6 h after intravenous administration of gadolinium, before EMS, and 2 years after the surgery. The enhanced perilymphatic space in the bilateral cochlea, vestibule, and canals was visualized and compared with that in the endolymphatic space by quantitatively scoring the scala vestibuli of the cochlea and by measuring the developing area of the vestibules quantitatively.Results: Gadolinium was present in the perilymph of the inner ear in the cochlea, vestibules, and canals of all patients. At the 2-year follow-up, 14 (73.68%) patients had vertigo control. Both before and 2 years after surgery, significant differences were observed in the scala vestibuli scores and the area of vestibular perilymph between the affected and healthy sides. The scala vestibuli scores and the area of vestibular perilymph, however, did not differ when comparing them before and after surgery.Conclusions: According to our results, endolymphatic hydrops was not significantly reduced by surgery. The mechanism by which EMS controls vertigo might be unrelated to the improvement in hydrops.

Хирургическое лечение опухоли эндолимфатического мешка из комбинированного доступа: клиническое наблюдение и обзор литературы

The article describes a clinical observation of a 17-year-old patient with an advanced tumor of the endolymphatic sac in the direction of the middle and posterior cranial fossae, the internal auditory meatus, and the cerebellopontine angle. After selective embolization of tumor afferent vessels, a combined transmastoid, translabyrinthine, and extended approach through the middle cranial fossa was used. The facial nerve is preserved along its entire length. The inferior cranial nerves remained intact when the mass was removed from the jugular foramen. Resection of the lower part of the tumor together with the sigmoid sinus, endolymphatic sac, and bulb of the jugular vein was performed after tamponade of the transverse and inferior petrosal sinus. The structure of the upper part of the tumor included: mastoid process, antrum, and tegmen tympani, which were resected after coagulation of the middle meningeal artery. The petrous part of the tumor was removed after preservation and mobilization of the internal carotid artery and visualization of the third (mandibular) branch of the trigeminal nerve. Repair of the bones of the base of the middle cranial fossa was carried out using the Medpor material. The postoperative cavity was obliterated with abdominal fat, and the external auditory meatus was tightly sutured using the cul-de-sac technique.

Anaesthetic Management of a Patient with Von-Hippel-Lindau Syndrome: A Conglomeration of Perplexities

Von-Hippel-Lindau (VHL) syndrome is an autosomal dominant disease with multisystem involvement. Tumours associated with VHL include, hemangioblastomas of the spine and brain, retinal capillary hemangioblastomas, renal cell carcinoma, pheochromocytoma, and neuroendocrine tumours of pancreas. We present a case of a 54 year old female second-degree uterovaginal prolapse scheduled for laparoscopic assisted vaginal hysterectomy. She was diagnosed with adult polycystic kidney disease, pheochromocytoma, parathyroid adenoma, vertebral hemangioma and multiple renal and hepatic cysts. Though genetic testing was not feasible, the co-existing systemic manifestations in this patient were strongly suggestive of Von Hippel Lindau syndrome. Owing to the multi-morbidities, central neuraxial block was deemed appropriate as opposed to general anaesthesia. In concert with the surgeons, it was decided to change the surgical plan to vaginal hysterectomy and avoid adrenaline infiltration at the surgical site, as it is known to precipitate arrythmias. We placed an intra-arterial catheter for continuous blood pressure monitoring before administration of the subarachnoid block and co-loaded the patient with fluids to avoid any drastic hypotension. The patient remained hemodynamically stable throughout the procedure, which could be attributed to extensive pre-operative work-up multi-disciplinary pre-operative optimization and synergistic management with surgical team. Providing anaesthesia to patients with multisystem involvement such as Von Hippel Lindau syndrome can be very challenging. Meticulous pre-anaesthetic evaluation and pre-operative optimization are often crucial. A multidisciplinary approach is often employed to achieve the best possible pre-operative functional status of these patients. Well-coordinated team with flexibility in management tailored to the patient helps achieve the best possible outcomes. Disclaimer: Informed consent was obtained from the patient prior to publication Main Points • Von-Hippel-Lindau (VHL) syndrome is an autosomal dominant disease with multisystem involvement; associated tumours include hemangioblastomas of the CNS, retinal capillary hemangioblastomas, renal cell carcinoma, pheochromocytoma, endolymphatic sac tumours of the middle ear, serous cystadenomas and neuroendocrine tumours of pancreas. • Providing anaesthesia to patients with multisystem involvement such as Von Hippel Lindau syndrome can be very challenging. Meticulous pre-anaesthetic evaluation and pre-operative optimization are often crucial. • A detailed anaesthetic plan, tailored to each patient, has to be formulated in elective cases, after an extensive work-up of the associated tumours. • Extensive pre-operative work-up, a multi-disciplinary approach towards pre-operative optimization and synergistic management with surgical team remains vital in minimizing peri-operative complications. • Anaesthetic implications are often at the nexus of surgical outcomes, hence, proper communication with the surgical team and arrival at a joint plan is crucial.

Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on the central nervous system.

Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant inherited syndrome that affects the germline of the VHL gene, a tumor suppressor gene. VHL disease is characterized by the multisystemic development of a variety of benign and malignant tumors, especially in the central nervous system (CNS). Such tumors include retinal and CNS hemangioblastomas, as well as endolymphatic sac tumors. The various tumor sites are responsible for the diversity of signs and symptoms related to the disease. The mean age at symptom onset is 33 years. Despite medical advances, the average life expectancy of patients with VHL disease is 49 years. Imaging plays a pivotal role in the clinical diagnosis and is essential to the follow-up of patients with VHL disease. This pictorial essay describes characteristic CNS manifestations of VHL disease-related tumors that all radiology residents should be aware of.

Surgical Management of Intractable Meniere's Disease.

Meniere's Disease (MD) is an inner ear disorder characterized by spontaneous recurrent vertigo, fluctuating sensorineural hearing loss, aural fullness and low-pitch tinnitus. Therapeutic management of MD includes dietary restriction and medical therapy. A minority of cases is characterized by frequent vertigo attacks, progressive hearing loss and persistent tinnitus even through the continuous medical treatments; this condition is called intractable MD and requires a therapeutic escalation from non-invasive medical treatment to surgical intervention. Invasive procedures include endolymphatic sac surgery, vestibular nerve section and labyrinthectomy. These procedures have a very high success rate on symptom control but may have a severe impact on the hearing function. However, the simultaneous combined approach of demolitive surgery and cochlear implantation may be a valid approach to treat symptoms of intractable MD and preserve hearing function. In the present study, we review current literature focusing on intractable MD to describe and discuss advantages and disadvantages of established and newly proposed surgical treatments for intractable MD.

Outcomes of Endolymphatic Sac Surgery for Meniere's Disease with and without Comorbid Migraine.

Purpose To explore outcomes of endolymphatic sac surgery for patients with Meniere's disease with and without the comorbid condition of migraine. Materials and Methods A retrospective chart review of adult patients undergoing endolymphatic sac surgery at a single tertiary care center from 1987 to 2019 was performed. All adult patients who failed medical therapy and underwent primary endolymphatic sac surgery were included. The main outcome measures were vertigo control and functional level scale (FLS) score. Patient characteristics, comorbidities, and audiometric outcomes were tracked as well. Results Patients with Meniere's disease and migraine had a stronger association with psychiatric comorbidities (64.29% vs. 25.80%, p=0.01), shorter duration of vertigo episodes (143 vs. 393 min, p=0.02), and younger age (36.6 vs. 50.8 yr, p=0.005) at the time of endolymphatic sac surgery. Postoperative pure tone averages and word recognition scores were nearly identical to preoperative baselines. Class A vertigo control (47.92%) was most common, followed by class B vertigo control (31.25%). The FLS score improved from 4.2 to 2.8 (p < 0.001). Both patients with and without migraine had classes A-B vertigo control (66.67% vs. 80.95%) without any statistically significant difference (p=0.59). Of the patients who required secondary treatment (10.42%), none had migraine. Conclusions Endolymphatic sac surgery is an effective surgical intervention for Meniere's disease with and without migraine. Patients with comorbid migraine tend to be younger and present with psychiatric comorbidities.

A Historical Perspective on Surgical Manipulation of the Membranous Labyrinth for Treatment of Meniere's Disease.

Meniere's disease is an inner ear disorder without a known cause. Endolymphatic hydrops is a swelling of the endolymph spaces that has been observed consistently on post-mortem histology in patients with a history of Meniere's disease but can occur in asymptomatic individuals and in association with other diseases. Since its discovery, Meniere's disease has been a disorder managed primarily by otolaryngologists. Surgical treatments, therefore, have accompanied attempts at medical management. Inspired by patients' sensations of ear fullness and later by the histologic findings of hydrops, surgeons began manipulating the membranous labyrinth to relieve episodes of vertigo while attempting to preserve hearing. This review highlights this history of manipulation of the membranous labyrinth. These procedures indicate a rich history of innovation that parallels developments in otologic surgery. The studies involving patients are uniformly retrospective, with some procedures performed first in animal models of endolymphatic hydrops. Many approaches were endorsed by eminent otologic surgeons. Surgeries on the endolymphatic sac are performed by some surgeons today; however, procedures on the membranous labyrinth resulted in similar symptomatic relief through a minimally invasive technique, in many cases performed using only local anesthetic. Episodic vertigo in patients with Meniere's disease is a distressing symptom, yet spontaneous remissions are common. The reports of procedures on the membranous labyrinth reviewed here consistently indicated fewer vertigo episodes. Variable degrees of hearing loss were common following these procedures, and many were abandoned. Additional innovative surgeries are inevitable, but we must understand better the relationships among endolymphatic hydrops, Meniere's disease pathophysiology, and patient symptoms.

Triple semicircular canal occlusion combined with endolymphatic sac decompression: An effective surgical strategy for vertigo control of intractable Meniere's disease.

Triple semicircular canal occlusion is an efficient strategy for vertigo control in patients with intractable Meniere's disease The surgery can block the movement of endolymph in the canals to eliminate vertigo attacks induced by position changing Patients with advanced stage MD suffered more from hearing deterioration postoperatively The aural fullness remission was satisfactory postoperative Vestibular rehabilitation is important and effective for vestibular function compensation, it should be recommended to all patients postoperatively.

3 Tesla MR imaging of the large endolymphatic duct and sac anomaly with audiological correlation

PurposeLarge endolymphatic duct and sac (LEDS) is one of the most common imaging abnormalities in congenital sensorineural hearing loss and is frequently seen with coexistent cochlear anomalies, especially incomplete partition type II. However, MRI findings of accompanying cochlear and especially modiolar dysplasias may be subtle. The purpose of this study is to evaluate the imaging findings of LEDS with high-resolution imaging at 3 T and correlate with the audiological data. Methods3 T temporal bone MRIs of 54 ears in 30 LEDS patients were retrospectively evaluated. The cochlear dysmorphism and modiolar deficiency were assessed qualitatively and quantitatively. The severity of LEDS anomaly, the signal changes within the LEDS and cochlea were also noted. The imaging findings were correlated to the audiological data. ResultsThe cochlea was abnormal in 77.8% of the ears with an isolated modiolar deficiency in 11.1%. Cochlea and modiolus were completely normal in 11.1% of the ears. In 63% of the ears X-distance was increased. T2 hypointensity within LEDS and cochlea were detected in 42.6%, and 7.4% of the ears, respectively. The median diameters of LEDS were higher in ears with severe to profound HL than ears with normal to moderate HL (p < 0.05). The X-distance, presence of T2 hypointensity within LEDS, and diameters of modiolus did not show statistical correlation with the audiographic data. ConclusionHigh-resolution 3 T imaging of patients with LEDS anomaly revealed a spectrum of cochlear anomalies, but up to 11.1% of the ears had no underlying anomaly despite severe (endolymphatic duct/sac) dilatation and/or profound HL.

RESPONSE TO LETTER TO THE EDITOR: "IS MENIÈRE'S DISEASE A CONTRAINDICATION TO STAPEDECTOMY?"

In Reply: We thank the authors for reading our article (1) with interest and for their valuable comments. We agree on the importance of properly differentiating the nature and etiology of vestibular complaints in any patient, especially in those in which multiple etiologies may be suspected. This is particularly relevant in the matter at hand, given that upwards of 30% of patients with otosclerosis report vestibular symptoms (2–7). Possible mechanisms include endosteal involvement of otosclerotic foci associated with vestibular hair cell loss (8), malfunction of the endolymphatic sac and duct (9), changes in the biochemical composition or radial flow of perilymph and endolymph (10,11), or the production of cupular deposits (12). Practically speaking, while there may be a variety of etiologies, the concomitance of otosclerosis and Menière's disease (MD) has been demonstrated, with the rate of symptomatic endolymphatic hydrops being nearly 30 times greater in otosclerosis patients compared with the general population. The importance of properly differentiating between MD and otosclerosis, not to mention any other vestibular disorder, is paramount in the initial evaluation and management of any dizzy patient. This becomes magnified when considering stapes surgery given the significant risk associated with violation of the oval window footplate in patients with endolymphatic hydrops (13). As discussed, distension of the saccule can cause close proximity or even adherence to the undersurface of the footplate, which puts the patient at risk for a dead ear should the saccule become violated during the fenestration process. For this reason, we adhere to the dictum proposed by McCabe in 1966 (6) that patients should demonstrate at minimum 6 months of medically stable Menière's disease without an episode of fluctuating hearing loss or vertigo before stapes surgery. In theory, this would indicate adequate control of endolymphatic pressure and could allow for resolution of saccular distention, thereby reducing the immediate surgical risk. As patients in our review were only offered stapes surgery following a minimum of 6 consecutive months of stable Menière's disease, our results may only be generalizable to similarly well-managed patients. With regards to evaluation and management, our institutional practice is in line with the American Academy of Otolaryngology–Head and Neck Surgery Clinical Practice Guidelines (14), which recommends against routine vestibular function testing or electrocochleography to establish the diagnosis of Menière's disease. We do routinely obtain audiograms in these patients who also undergo clinical vestibular testing as part of our standard physical examination protocol. As such, we follow the guideline recommendations to diagnose patients meeting criteria of probable or definite Menière's disease. Those with an uncertain diagnosis may go on to have formal electrophysiologic vestibular testing. Following our review, all patients included for analysis met criteria for definite MD, however there was not enough compelling electrophysiologic vestibular testing data to report. As the authors suggest, there is growing evidence to support the use of video head impulse testing (vHIT) and vestibular evoked myogenic potentials (VEMPs) in addition to caloric testing to more comprehensively evaluate the vestibular system (15,16). As we use clinical outcomes to guide therapy, we do not routinely order or track changes in electrophysiologic vestibular testing. As such, the patients reported in our study were counseled on surgical options and risks of otosclerosis without routine vestibular testing. We acknowledge the limitations of our sample size and hope that this report is a catalyst for further study into this difficult to manage patient population. Evidence regarding the role of a comprehensive vestibular evaluation for the selection of appropriate surgical patients would be a welcome addition to our shared body of knowledge, however this was outside the scope of this report. Our study aim was to review the surgical outcomes of the relatively rare stapedotomy in patients with concomitant otosclerosis and Menière's disease. The results support the conclusion that medically stable Menière's disease need not be considered an absolute contraindication to stapes surgery, as some smaller studies have previously suggested (13). Despite this conclusion, we continue to share your expressed caveat that such cases should be taken on judiciously.

Interventions for Menière’s disease: an umbrella systematic review

ObjectivesTo systematically review the efficacy of interventions for Menière’s disease (MD) to report clinical implications of the results and to identify areas for future valuable research.MethodsIn line with the Preferred...

Expression of VHL, VEGF and HIF-1α in endolymphatic sac tumors

Objective: To investigate the expression of von Hippel-Lindau (VHL), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α) in endolymphatic sac tumor (ELST) and its clinical significance, and to analyze its association with VHL gene mutation. Methods: Twenty-four cases of ELST, which were surgically resected and diagnosed by pathological examination in Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China during 2012-2020, were recruited as the ELST group, and 24 cases of otitis media diagnosed in the same hospital were selected as the control group. The expression of VHL, VEGF, and HIF-1α was assessed using EnVision immunohistochemical staining and compared between the ELST and control groups. Sanger sequencing was performed to detect the VHL mutation status in 24 ELSTs. The correlations among VHL, VEGF and HIF-1α expression were analyzed. The associations of VHL, VEGF and HIF-1α expression with age of onset, gender, tumor size, bone invasion and clinical stage in ELST were also analyzed. Results: The expression rate of VHL in the ELST group was significantly lower than that in the control group (P<0.05), but the expression rates of VEGF and HIF-1α in the ELST group were significantly higher than those in the control group (P<0.05). VHL expression was inversely correlated with VEGF and HIF-1α expression. The expression of VEGF and HIF-1α was associated with bone invasion and clinical stage (P<0.05), but the expression of VHL, VEGF and HIF-1α had no significant associations with the age of onset, gender, or tumor size of ELST (P>0.05). Conclusions: The expression of VHL is decreased while that of VEGF and HIF-1α increased in ELST. Expression of VHL is inversely correlated with that of VEGF and HIF-1α. The expression of VEGF and HIF-1α is correlated with bone invasion and clinical stage. Thus, VEGF and HIF-1α may be therapeutic targets of ELST.