Meniere's Disease Patients with Distinct Sac Pathoanatomic Findings React Differently to Endolymphatic Duct Blockage.

OBJECTIVES: To explore the possible difference in response to endolymphatic duct blockage (EDB) treatment in patients with Meniere's disease (MD) with distinct pathoanatomic characteristics of the sac. METHODS: In a total of 24 patients with MD receiving EDB treatment, the dynamics of the vertigo attack, hearing, vestibular function, and endolymph hydrops (EH) before surgery and 40 months following surgery in patients with normoplastic extraosseous portion of endolymphatic sac (eES) were compared with that in patients with atrophic eES. RESULTS: A higher prevalence of complete vertigo control, better cochlear and vestibular function, and lower endolymph to vestibule-volume ratio were found in patients with normoplastic eES than in those with atrophic eES. Moreover, the reversal of EH was found in a total of six patients in normoplastic eES group, but no reversal of EH was detected in the atrophic eES group after surgery. CONCLUSIONS: A difference in response to EDB treatment was shown in the MD patients with normoplastic eES and those with atrophic eES; the reversal of EH was found in the normoplastic eES group, but not in the atrophic eES group after surgery, suggesting two distinct pathologies in the eESs may underlie the pathogenesis of EH in two subgroups of MD patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2761-2769, 2023.

A three-dimensional analysis of the endolymph drainage system in Ménière disease.

OBJECTIVES/HYPOTHESIS: To measure the volume of the endolymph drainage system in temporal bone specimens with Ménière disease, as compared with specimens with endolymphatic hydrops without vestibular symptoms and with nondiseased specimens STUDY DESIGN: Comparative human temporal bone analysis. METHODS: We generated three-dimensional models of the vestibular aqueduct, endolymphatic sinus and duct, and intratemporal portion of the endolymphatic sac and calculated the volume of those structures. We also measured the internal and external aperture of the vestibular aqueduct, as well as the opening (if present) of the utriculoendolymphatic (Bast's) valve and compared the measurements in our three study groups. RESULTS: The volume of the vestibular aqueduct and of the endolymphatic sinus, duct, and intratemporal endolymphatic sac was significantly lower in the Ménière disease group than in the endolymphatic hydrops group (P <.05). The external aperture of the vestibular aqueduct was also smaller in the Ménière disease group. Bast's valve was open only in some specimens in the Ménière disease group. CONCLUSIONS: In temporal bones with Ménière disease, the volume of the vestibular aqueduct, endolymphatic duct, and intratemporal endolymphatic sac was lower, and the external aperture of the vestibular aqueduct was smaller as compared with bones from donors who had endolymphatic hydrops without vestibular symptoms and with nondiseased bones. The open status of the Bast's valve in the Ménière disease group could be secondary to higher retrograde endolymph pressures caused by smaller drainage systems. These anatomic findings could correlate with the reason that some patients with hydrops develop clinical symptoms, whereas others do not. LEVEL OF EVIDENCE: N/A Laryngoscope, 127:E170-E175, 2017.

Stria vascularis and cochlear hair cell changes in syphilis: A human temporal bone study.

OBJECTIVE: To observe any changes in stria vascularis and cochlear hair cells in patients with syphilis. MATERIALS AND METHODS: We examined 13 human temporal bone samples from 8 patients with syphilis (our syphilis group), as well as 12 histopathologically normal samples from 9 age-matched patients without syphilis (our control group). We compared, between the two groups, the mean area of the stria vascularis (measured with conventional light microscopy connected to a personal computer) and the mean percentage of cochlear hair cell loss (obtained from cytocochleograms). RESULTS: In our syphilis group, only 1 (7.7%) of the 13 samples had precipitate in the endolymphatic or perilymphatic spaces; 8 (61.5%) of the samples revealed the presence of endolymphatic hydrops (4 cochlear, 4 saccular). The mean area of the stria vascularis did not significantly differ, in any turn of the cochlea, between the 2 groups (P>0.1). However, we did find significant differences between the 2 groups in the mean percentage of outer hair cells in the apical turn (P<0.026) and in the mean percentage of inner hair cells in the basal (P=0.001), middle (P=0.004), and apical (P=0.018) turns. In 7 samples in our syphilis group, we observed either complete loss of the organ of Corti or a flattened organ of Corti without any cells in addition to the absence of both outer and inner hair cells. CONCLUSION: In this study, syphilis led either to complete loss of the organ of Corti or to significant loss of cochlear hair cells, in addition to cochleosaccular hydrops. But the area of the stria vascularis did not change.

Comparison of noninvasive evaluation of endolymphatic space in healthy volunteers in different age groups using magnetic resonance imaging.

CONCLUSIONS: Noninvasive standard evaluation of normal endolymphatic space and endolymphatic hydrops using magnetic resonance imaging (MRI) in various age groups is reported for the first time. OBJECTIVE: To compare the standard evaluation of endolymphatic space in healthy volunteers in the cochlea and the vestibule among different age groups by applying noninvasive intratympanic gadolinium (Gd) perfusion through the eustachian tube and three-dimensional fluid-attenuated inversion recovery MRI (3D-FLAIR MRI). METHODS: This was a prospective study. 3D-FLAIR MRI was performed with a 3 T unit 24 h after intratympanic administration of Gd through the eustachian tube in 60 healthy volunteers aged 20-55 years. Pure-tone test and tympanometry were performed 24 h before and 1 week after Gd administration. RESULTS: There was no significant difference in the ratios of the area of the endolymphatic space to that of the fluid space in the cochlea and the vestibule between males and females, or among 20-30-, 31-44-, and 45-55-year-old healthy volunteers. In 20-55-year-old healthy volunteers, the normal value of the endolymphatic space in the cochlea ranged between 7% and 27%, and that in the vestibule was between 17% and 39%. No significant changes in pure-tone test or tympanometry were noted.

Pituitary carcinoma with endolymphatic sac metastasis.

Pituitary carcinoma is characterized by the presence of a metastatic lesion(s) in a location non-contiguous with the original pituitary tumor. The mechanism(s) of malignant transformation are not known. A 15 year-old male was diagnosed in 1982 with a pituitary macroadenoma and acromegaly (random GH 67 ng/ml and no suppression by oral glucose). His prolactin was normal between 18 and 23 ng/ml. Transcranial resection in July 1983 was followed by radiation therapy. The tumor was immunopositive for GH and prolactin. The proliferation MIB-1 index was 0-1%. With aqueous Octreotide 100 mcg 4× daily both GH and IGF-1 became normal. The patient was lost to follow-up and was treated by his local physician. In 2001, his IGF-1 level was 1271 ng/ml, and his random GH was 1.8-2.4 ng/ml by ILMA despite progressive increase in the dose of Sandostatin LAR to 140 mg/month in divided doses. Prolactin remained normal or minimally increased between 15 and 25 ng/ml. In 2009 he was diagnosed with the tumor in the location of left endolymphatic sac. Histological examination showed low grade pituitary carcinoma strongly immunopositive for prolactin but negative for GH. MIB-1 antibody labeled 0-5% cells. In 2012 endoscopic resection of the pituitary tumor remnant was attempted. Immunohistochemical stains were strongly immunopositive for both prolactin and GH, similar to his original pituitary tumor. The MIB-1 proliferation index was low from 0 to 1%. To our knowledge this is the first case of pituitary carcinoma in the endolymphatic sac region. The dichotomy between the cell population of the pituitary lesion (GH/prolactin producing) and the metastasis (purely prolactin-producing) may suggest that the metastatic pituitary lesion derived from a clone distinct from the original one.

Semi-quantification of endolymphatic size on MR imaging after intravenous injection of single-dose gadodiamide: comparison between two types of processing strategies.

PURPOSE: Many inner ear disorders, including Ménière's disease, are believed to be based on endolymphatic hydrops. We evaluated a newly proposed method for semi-quantification of endolymphatic size in patients with suspected endolymphatic hydrops that uses 2 kinds of processed magnetic resonance (MR) images. METHODS: Twenty-four consecutive patients underwent heavily T2-weighted (hT2W) MR cisternography (MRC), hT2W 3-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) with inversion time of 2250 ms (positive perilymph image, PPI), and hT2W-3D-IR with inversion time of 2050 ms (positive endolymph image, PEI) 4 hours after intravenous administration of single-dose gadolinium-based contrast material (IV-SD-GBCM). Two images were generated using 2 new methods to process PPI, PEI, and MRC. Three radiologists contoured the cochlea and vestibule on MRC, copied regions of interest (ROIs) onto the 2 kinds of generated images, and semi-quantitatively measured the size of the endolymph for the cochlea and vestibule by setting a threshold pixel value. RESULTS: Each observer noted a strong linear correlation between endolymphatic size of both the cochlea and vestibule of the 2 kinds of generated images. The Pearson correlation coefficients (r) were 0.783, 0.734, and 0.800 in the cochlea and 0.924, 0.930, and 0.933 in the vestibule (P<0.001, for all). In both the cochlea and vestibule, repeated-measures analysis of variance showed no statistically significant difference between observers. CONCLUSION: Use of the 2 kinds of generated images generated from MR images obtained 4 hours after IV-SD-GBCM might enable semi-quantification of endolymphatic size with little observer dependency.

Carcinoma del saco endolinfático: a propósito de un caso / Endolymphatic sac carcinoma: a case report

No disponible

Blockage of longitudinal flow in Meniere's disease: A human temporal bone study.

CONCLUSION: Blockage of the endolymphatic duct is a significant finding in Meniere's disease. The position of the utriculo-endolymphatic valve (UEV) and blockage of the ductus reuniens in the temporal bones were not found to be directly indicative of Meniere's disease. OBJECTIVE: Comparison of blockage of the longitudinal flow of endolymph between ears affected by Meniere's disease and normal ears. METHODS: We examined 21 temporal bones from 13 subjects who had Meniere's disease and 21 normal temporal bones from 12 controls. RESULTS: The endolymphatic duct was blocked in five (23%) ears affected by Meniere's disease (p = 0.016). The utricular duct was blocked in 16 (76%) ears affected by Meniere's disease and 11 (52%) normal ears (p = 0.112). The saccular duct was blocked in 6 (28%) of ears affected by Meniere's disease and 16 (76%) normal ears (p = 0.001). The ductus reuniens was blocked in 10 (47%) ears affected by Meniere's disease and 10 (47%) normal ears (p = 1.000).

Meniere's disease: new concepts, new treatments.

Our understanding of Meniere's disease is being revamped. For decades, the condition was thought to be caused by excessive fluid retention (hydrops) in the endolymphatic spaces of the inner ear, which led to tears or ruptures of the membranous structures that affect hearing and balance. More recently, research has shown that hydrops is not always associated with Meniere's and ought not to be considered the ultimate cause of its symptoms. New theories center on the fact that Meniere's disease may not have a single cause but may well be a common endpoint of a variety of anatomic or physiologic variables, including ischemic or even autoimmune injuries. This article describes the new thinking about Meniere's and explains why current treatment approaches, although they are based on outdated understanding, may still be valuable for alleviating symptoms in some patients.

The intravestibular source of the vestibular aqueduct. II: its structure and function clarified by a developmental study of the intra-skeletal channels of the otic capsule.

CONCLUSION: A developmental histologic study of the otic capsule indicates that it grows a system of lamellar bone with abundant interconnecting intraosseous channels. These include the 'cartilage canals' in the cartilage model, the chondro-osseous and Haversian-like (Volkmann's) canals in the ossified otic capsule, the fissula ante fenestram, which seems to function as a lifelong manufacturer of the latter two channels, and the inner layer (vestibular arch) of the vestibular aqueduct, which is a complex series of Volkmann's canals and microcanals. Chemical changes, possibly produced by breakdown of cells within the channels, may provide a homeostatic environment for the functions of hearing and balance that take place in the endolymphatic fluid. OBJECTIVES: We studied the development of the otic capsule to clarify the cellular appearances that we had previously described in the normal vestibular arch and the changes in that structure in Ménière's disease. METHODS: Step sections from 84 temporal bones, including those from fetuses, children and adults from a variety of ages were examined histologically. RESULTS: Cartilage canals, bringing blood vessels and mesenchymal cells from perichondrium to the depths of the cartilage model to mediate ossification, are found early in fetal life and disappear when ossification is complete at about 24 weeks. The otic capsule is formed of chondro-osseous canals, which are composed of trabeculae of mineralized cartilage lacunae containing mesenchymal cells that undergo ossification (globuli ossei); also Volkmann's canals (like Haversian canals in long bones but multidirectional), which are produced from osteoblasts. The lumina of the latter frequently link up with chondro-osseous canals. Lamellar bone forms the background of the otic capsule. The fissula ante fenestram is present from early in the cartilage model and then throughout life. It appears to mediate bone production and the new formation of chondro-osseous channels and Volkmann's canals. The internal layer of the vestibular aqueduct (vestibular arch) is seen in the cartilage model of the otic capsule (present in early fetal life) as a vascular layer of perichondrally derived connective tissue (not cartilage) surrounding the endolymphatic duct. When endochondral ossification starts, the bone from the adjoining cochlear and vestibular sides embrace this connective tissue layer to form the outer bony layer of the vestibular aqueduct. Osteoblasts then fill the inner layer with lamellar bone and macro- and mini-Volkmann's canals. At 1 year osteoblasts in the walls of macro-Volkmann's canals, proliferating thereafter throughout life, produce large numbers of microcanals. It is possible that slow breakdown of these osteoblasts and of similar cells in the canals of the otic capsule proper may contribute to the homeostasis of the endolymphatic duct and that of the rest of the membranous labyrinth, respectively.

Image evaluation of endolymphatic space in fluctuating hearing loss without vertigo.

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

The intravestibular source of the vestibular aqueduct: Its structure and pathology in Ménière's disease.

CONCLUSION: We describe a thin, highly vascular layer of mineralized cartilage, which surrounds most of the endolymphatic duct. In the normal ear this may act in helping to control the chemical composition of endolymph. In Ménière's disease (MD) there is a marked apoptotic change among the mineralized cartilage cells of this layer, which seems to be associated also with the deposition of a pathological substance in the walls of many blood vessels. This may lead to serious chemical change in the nearby endolymph and so provoke the symptoms of MD. OBJECTIVES: Endolymphatic hydrops is found in all cases of MD, but is not specific for that condition. We sought a cellular change in the vicinity of the saccule that might be more specific than the lesion of endolymphatic hydrops and thus lead to a more successful management of the disease. MATERIALS AND METHODS: We examined stained step sections of 33 autopsy temporal bones from 20 cases of MD, particularly in the region of the vestibule, and compared the changes with those found in a similar region of 65 temporal bones taken from randomly selected cases of non-Ménière conditions. RESULTS: In all temporal bones there was a well-demarcated region of the posterior vestibule, which formed a skeletal arch around the opening of the tunnel of the vestibular aqueduct into which the endolymphatic duct entered from the vestibule. This 'vestibular arch' was composed mainly of blood vessels and mineralized chondrocytes. The inner skeletal layer surrounding the course of most of the endolymphatic duct in the tunnel of the vestibular aqueduct was composed of the same tissue and was in fact continuous with the vestibular arch. In the non-Ménière temporal bones the mineralized chondrocytes were congregated around normal thin-walled blood vessels and small numbers of them seemed to be undergoing apoptosis in this vicinity. In all of the MD temporal bones, except five in which the vestibular arch was either absent or atrophic, we found pronounced changes of apoptosis among the mineralized cartilage cells and these were associated with proliferative changes in blood vessels in which a bluish-staining translucent deposit, possibly mineralization of the vascular wall, was prominent.

Can magnetic resonance imaging provide clues to the inner ear functional status of enlarged vestibular aqueduct subjects with PDS mutation?

OBJECTIVES: The goal of this study was to characterize the signal intensity (SI) pattern in the endolymphatic duct/sac from T2-weighted spin echo magnetic resonance (MR) images and T2*-weighted 3-dimensional (3-D) constructive interference in steady state (CISS) MR images that were obtained from a homogenous group of patients with an enlarged vestibular aqueduct (EVA) associated with SLC264 (PDS) mutations. STUDY DESIGN: A retrospective study. SETTING: Tertiary referral center. PATIENTS: Eleven subjects (22 ears), with at least 1 SLC26A4 mutation and bilateral EVA confirmed by temporal bone computed tomography, were enrolled. INTERVENTION: The MR images of 22 ears were reviewed retrospectively. MAIN OUTCOME MEASURES: The SI of the endolymphatic sac (ES) from 2 sequences were compared and reviewed. The presence of anomalies of the vestibule were also evaluated. In addition, the caloric test results were also reviewed to characterize the vestibular function in a subset of our cohort (12 ears). RESULTS: T2*-weighted 3-D CISS MR images revealed a more variable SI in the enlarged endolymphatic system than did the T2-weighted images. There was a hierarchy for the order of SI loss from the endolymphatic system on the T2*-weighted 3-D CISS MR images. There were 3 cases where the SI loss from the intraosseous ES, on the T2*-weighted 3-D CISS images, was associated with an abnormal caloric response. CONCLUSION: The SI of the ES observed on T2*-weighted 3-D CISS images of EVA patients, with SLC26A4 mutations, showed a distinctive pattern, and the results from this study suggest a potential role for the MR imaging in providing physicians with better information about the functional status of the inner ear.

A mouse model with postnatal endolymphatic hydrops and hearing loss.

Endolymphatic hydrops (ELH), hearing loss and neuronal degeneration occur together in a variety of clinically significant disorders, including Meniere's disease (MD). However, the sequence of these pathological changes and their relationship to each other are not well understood. In this regard, an animal model that spontaneously develops these features postnatally would be useful for research purposes. A search for such a model led us to the Phex Hyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (Phex Hyp-Duk/Y) was previously reported to exhibit various abnormalities during adulthood, including thickening of bone, ELH and hearing loss. The reported inner-ear phenotype was suggestive of progressive pathology and spontaneous development of ELH postnatally, but not conclusive. The main focuses of this report are to further characterize the inner ear phenotype in Phex Hyp-Duk/Y mice and to test the hypotheses that (a) the Phex Hyp-Duk/Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the Phex Hyp-Duk/Y mouse is associated with obstruction of the endolymphatic duct (ED) due to thickening of the surrounding bone. Auditory brainstem response (ABR) recordings at various times points and histological analysis of representative temporal bones reveal that Phex Hyp-Duk/Y mice typically develop adult onset, asymmetric, progressive hearing loss closely followed by the onset of ELH. ABR and histological data show that functional degeneration precedes structural degeneration. The major degenerative correlate of hearing loss and ELH in the mutants is the primary loss of spiral ganglion cells. Further, Phex Hyp-Duk/Y mice develop ELH without evidence of ED obstruction, supporting the idea that ELH can be induced by a mechanism other than the blockade of longitudinal flow of endolymphatic fluid, and occlusion of ED is not a prerequisite for the development of ELH in patients.

[Large endolymphatic duct and sac syndrome : part 2: clinical manifestations]. / Der erweiterte Ductus und Saccus endolymphaticus : Teil 2: Klinische Manifestationen.

OBJECTIVE: The aim of this study was to clarify the clinical course of large endolymphatic duct and sac syndrome (LEDS). Although LEDS is the most common form of radiologically detectable inner ear malformation associated with sensorineural hearing loss (SNHL), it is relatively unknown in the German-speaking countries. We hoped to derive useful pointers for clinical care. METHODS: We evaluated the clinical audiometric records and imaging findings of 169 patients with clinically suspected inner ear malformation seen between 1994 and 2003. Following identification of all LEDS cases, we serially investigated the anamnestic and functional data with regard to severity and course. RESULTS: Among 169 patients, 17 (median age 12 years; 12 females) showed LEDS. A total of 28 ears were affected. Clinically, most cases were of prelingual or perilingual onset and displayed steady or fluctuatingly progressive severe SNHL with emphasis on the high frequencies or deafness. Episodes of sudden hearing loss were relatively frequent. No correlation could be demonstrated between the severity of morphological changes and the degree of SNHL. CONCLUSION: Progression of SNHL and episodes of sudden hearing loss were seen mainly in late childhood or adolescence. This should be taken into account when informing and advising patients and planning therapy.

[Large endolymphatic duct and sac syndrome (LEDS) : part I: analysis of imaging findings]. / Der erweiterte Ductus und Saccus endolymphaticus : Teil 1: Analyse bildgebender Befunde.

OBJECTIVE: Large endolymphatic duct and sac (LEDS) syndrome is the most common radiologically detectable form of inner ear malformation (IEM) associated with sensorineural hearing loss (SNHL). Nevertheless, it is relatively unknown in the German-speaking countries. METHODS: Among all patients referred from ear, nose, and throat specialists to the radiology department with clinically suspected IEM between 1994 and 2003, we identified the cases of LEDS. The retrospective study included clinical records, high-resolution computed tomography, and magnetic resonance imaging. RESULTS: Of 169 patients, 17 (median age 12 years; 12 females) showed LEDS. A total of 28 ears were affected. Ten patients (6%; 15 ears) had isolated LEDS, while seven patients showed additional IEM (4%; 13 ears). The most frequent of these was dysplastic vestibule (13/13 ears), followed by Mondini deformity (10/13 ears) and dilated semicircular canals (7/13 ears). Three of 13 ears revealed severe IEM of the cochlea, vestibule, and semicircular canals. No correlation could be demonstrated between the severity of morphological changes and the degree of SNHL. CONCLUSION: LEDS may be an underestimated cause of SNHL. Imaging is necessary for a confident diagnosis.

A new animal model for Ménière's disease.

CONCLUSION: A new murine model for the study of Ménière's disease has been developed by treatment with both lipopolysaccharide (LPS) and aldosterone. Induction of vestibular dysfunction in the hydropic animal model may entail additional stress such as reduced inner ear blood flow, and sudden acute changes in endolymph volume and/or pressure. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, showing closer resemblance to the pathophysiological process in Ménière's disease. MATERIALS AND METHODS: Adult CBA/J mice were treated by intratympanic injection of LPS, intraperitoneal injection of aldosterone, or injection of both LPS and aldosterone. Morphological analyses were performed in the cochlea and endolymphatic sac. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops. Those treated with both LPS and aldosterone showed reversible vestibular dysfunction after the intratympanic injection of epinephrine.

Evaluation and management of endolymphatic sac and duct tumors.

The endolymphatic sac tumor is a slow-growing, locally aggressive neoplasm that originates from the epithelium of the endolymphatic sac and duct. Disease progression can lead to profound sensorineural hearing loss, posterior fossa invasion, brainstem compression, drop metastasis, and eventual death. Early diagnosis and surgical attention are the primary objectives in the management of patients who have endolymphatic sac tumor. This article describes the latest rationale and techniques for hearing preservation surgery and a review of the latest developments surrounding this disease entity.