Consensus on MR Imaging of Endolymphatic Hydrops in Patients With Suspected Hydropic Ear Disease (Meniere).

Endolymphatic hydrops (EH) is considered the histological hallmark of Meniere's disease. Visualization of EH has been achieved by special sequences of inner ear magnetic resonance imaging (MRI) with a gadolinium-based contrast agent via intravenous or intratympanic administration. Although it has been applied for more than 10 years since 2007, a unified view on this technique has not yet been achieved. This paper presents an expert consensus on MRI of endolymphatic hydrops in the following aspects: indications and contra-indications for patient selection, methods of contrast-agent administration (intravenous or intratympanic), MRI sequence selection, the specific scanning parameter settings, and standard image evaluation methods and their advantages and disadvantages. For each part of this consensus, a comment is attached to elucidate the reasons for the recommendation.

Clinical high-resolution imaging and grading of endolymphatic hydrops in Hydropic Ear Disease at 1.5 T using the two-slice grading for vestibular endolymphatic hydrops in less than 10 min.

BACKGROUND: Hydropic Ear Disease (Menière) is one of the most common inner ear disorders and one of the most common causes of vertigo attacks. The underlying pathology is a distension of the endolymphatic space of the inner ear, termed endolymphatic hydrops. However, the unequivocal morphologic confirmation of ELH has been restricted to post-mortem histologic analysis until 2007, when the first clinical MR imaging report demonstrated ELH in living patients with Menière's disease at 3 T combined with intratympanic application of contrast. Imaging techniques have since then evolved further. However, a high magnetic field strength of 3 T has consistently been mandatory for reliable clinical imaging of ELH. This limitation has significantly prevented ELH imaging from being widely available across different health care systems around the world. With the aim of filling this gap, in the present study, we aim to describe the feasibility of ELH imaging at 1.5 T in clinical practice and to develop a dedicated grading system for cochlear and vestibular ELH for MR imaging at 1.5 T. METHODS: In this retrospective study, we examined 30 patients with suspected hydropic ear disease undergoing diagnostic MR imaging. Contrast agent was diluted eightfold in saline solution and unilaterally applied by intratympanic injection as described previously. MRI scanning was performed using a 16-channel head coil on a 1.5 T Achieva Philips Medical Systems Scanner using a 3D FLAIR sequence. For the cochlea, a 3-stage grading was developed. For the vestibulum, a 4-stage grading based on two axial slices was developed by analysing both the superior and the inferior part of the vestibulum. The presence of hydropic herniation of the endolymphatic space into the posterior crus of the horizontal semicircular canal was evaluated. RESULTS: In all 30 patients, the perilymphatic fluid spaces of the inner ear showed clear and high signal intensity, while the endolymphatic space was not enhanced. In all patients, the vestibular endolymphatic space could be clearly delineated and differentiated from the perilymphatic space. Analysis of the cochlear endolymphatic space revealed no evidence of ELH in 7 patients, a grade 1 cochlear ELH in 11 patients and a grade 2 cochlear ELH in 12 patients. Analysis of the vestibular endoylmphatic space revealed no evidence of ELH in 8 patients, a grade 1 vestibular ELH in 5 patients, a grade 2 vestibular ELH in 9 patients and a grade 3 vestibular ELH in 8 patients. Three patients showed a clear hydropic herniation of the vestibular endolymphatic space into the posterior non-ampullated crus of the horizontal SCC. CONCLUSION: In summary, the findings presented in this study offer an easy, reliable and universally available technique of ELH imaging for diagnostic management of patients with suspected Hydropic Ear Disease.

Menière's disease.

Menière's disease causes paroxysmal rotatory vertigo, due to endolymphatic hydrops, an accumulation of endolymph in the endolymphatic space of the labyrinth. Its major symptoms are attacks of rotatory vertigo lasting minutes to hours, with unilateral hearing loss, tinnitus and aural fullness. As the disease progresses, attacks happen less often, but hearing loss and tinnitus gradually become permanent. Neuro-otological complications may develop, such as benign paroxysmal positional vertigo, vestibular drop attacks and bilateral vestibulopathy. The diagnosis of Menière's disease is based on the typical clinical picture and typical findings on the audiogram. Furthermore, it is now possible to diagnose it by MR of the inner ear. Long-term management has several steps, including diet, diuretics, intratympanic injection of corticosteroid or gentamicin and surgery (endolymphatic sac surgery, grommet insertion, surgical labyrinthectomy).

Laterality of Audiovestibular Symptoms Predicts Laterality of Endolymphatic Hydrops in Hydropic Ear Disease (Menière).

BACKGROUND: For clinical confirmation of the diagnosis of hydropic ear disease (HED) (Menière) by MR imaging, two routes of contrast enhancement of the perilymphatic space are currently being used: intratympanic and intravenous. While unilateral intratympanic contrast application generally enables a higher perilymph signal intensity and image quality, the intravenous route allows for imaging of both inner ears simultaneously. It is conceivable that intratympanic contrast application to one ear would result in a failure to detect endolymphatic hydrops in a given patient if the hydrops is present only in the other ear. Therefore, in this study we examined the question whether the ear with the greater degree of endolymphatic hydrops may be predicted based on clinical features. METHODS: Retrospective study of 50 patients with HED confirmed on MR imaging. Three tesla MR imaging with 3D fluid attenuated inversion recovery 4 hours after intravenous gadolinium contrast application was used to detect endolymphatic hydrops. The index ear was defined by auditory symptoms during attacks, low frequency hearing loss, and caloric canal paresis. RESULTS: In all patients the ear with more severe symptoms corresponded with the ear showing the more severe hydrops on MR imaging. CONCLUSION: In summary, in this study population the degree of low-frequency hearing loss (250 Hz-1 kHz) in combination with auditory symptoms during attacks identified the ear with the greater extent of endolymphatic hydrops in all patients. In conclusion, intratympanic contrast application to the index ear seems to be sufficient to confirm the diagnosis of HED (Menière) on MR imaging.

Complex human adenoid tissue-based ex vivo culture systems reveal anti-inflammatory drug effects on germinal center T and B cells.

BACKGROUND: Human immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in secondary lymphoid organs, such as in the case of germinal center (GC) T follicular helper (Tfh) cells and GC B cells. METHODS: We developed a versatile ex vivo lymphoid organ culture platform that is based on human pharyngeal tonsils (adenoids) and allows for drug testing. We systematically phenotyped Tfh and GC B cell subsets in explant- and suspension cultures using multicolor flow cytometry and cytokine multiplex analysis. FINDINGS: Phenotypic changes of certain ex vivo cultured immune cell subsets could be modulated by cytokine addition. Furthermore, we optimized an activation-induced marker assay to evaluate the response to T cell stimulation. We provide proof-of-concept that Tfh and GC B cells could be modulated in these cultures by different anti-inflammatory drugs in unstimulated states and upon activation with vaccine-derived antigens. For example, GC B cells were lost upon CD40L blockade, and clinically approved JAK inhibitors impacted Tfh and GC B cells, including down-regulation of their key transcription factor BCL6. BCL6 regulation was affected by IL-6 signaling in T cells and IL-4 in B cells, respectively. Furthermore, we demonstrated that JAK signaling and TNF signaling contributed to the stimulation-induced activation of tonsil-derived T cells. INTERPRETATION: Our optimized methods, assays, and mechanistic findings can contribute to a better understanding of human GC responses. These insights may be relevant for improving autoimmune disease therapy and vaccination efficacy. FUNDING: This work was supported by a project grant under the joint research cooperation agreement of LMU Munich, LMU University Hospital, and Sanofi-Aventis Deutschland GmbH, as well as by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Emmy Noether Programme BA 5132/1-1 and BA 5132/1-2 (252623821), SFB 1054 Project B12 (210592381), and SFB 914 Project B03 (165054336).

Influence of Cochlear Implantation on Postural Control and Risk of Falls.

BACKGROUND: Cochlear implantation is an important method of hearing rehabilitation. Earlier studies have shown the influence of implantation on the vestibular system. However, until now, the effect of hearing rehabilitation with cochlear implants (CI) on postural control and body stability has not been sufficiently studied. OBJECTIVE: To analyse the effect of hearing rehabilitation with activated CI and different sound inputs (music, speech text, and white noise) on postural control and risk of falls after implantation. METHODS: This was a prospective clinical trial that included 33 adult patients with at least 6 months' use of a CI (mean time after implantation = 23 months). All patients underwent a standard or geriatric (for patients >60 years) balancing deficit test protocol with a mobile posturography system (VertiGuard®) in different situations (CI deactivated/activated and different sound inputs). As the main outcome measure, the risk of falls (%) after each protocol was calculated by evaluating body sway both forward to backward and side to side (°/s). RESULTS: With the CI deactivated, the mean risk of falls was 45.5%. After activation of the CI, there was a small decrease in the mean risk of falls, but it was statistically significant. With an additional sound input (music or speech text) this decrease was more pronounced: 42.0 and 42.4%, respectively. This effect seems to be more pronounced in older patients. Regarding the individual patients, 72% had an improvement in the risk of falls with an activated CI, and 28% had a slight deterioration. An activated CI accompanied by sound input (music) further improved the individual risk of falls. CONCLUSIONS: Compared with prior research, this study found that the risk of falls after implantation decreased over a longer time period. Furthermore, the use of a CI and different sound inputs had a positive effect on postural control. These findings support the need for optimal hearing rehabilitation, especially in elderly patients. Although this effect is relatively small, it is important to consider for further studies that rehabilitation with CI may reduce the risk of falls. While the auditory system supposedly contributes to postural control only to a small degree and the mechanism is still poorly understood, further studies with bigger samples are warranted to clarify these effects.

Correction to: Clinical manifestations of hydropic ear disease (Menière's).

In the original publication, Fig. 1 was incorrectly published with incomplete legends.

High-Frequency Horizontal Semicircular Canal Function in Certain Menière's Disease.

OBJECTIVES: To characterize video head impulse testing (vHIT) in definitive Menière's disease and to investigate the relationship between vHIT results and other audiovestibular function tests. DESIGN: Fifty-four patients with certain Menière's disease, that is, patients with clinically definite Menière's disease and endolymphatic hydrops visualized by locally enhanced inner ear MR imaging, were recruited for this study. All patients underwent vHIT. The vestibular-ocular reflex gain at 60 ms and refixation saccades were the outcome parameters measured. Saccades were characterized by determining the saccade frequency, their mean latency, and their mean velocity. RESULTS: Seven of 54 patients had bilateral normal vHITs. Clearly pathologically vHITs with decreased gain and refixation saccades were observed in further seven patients. The majority of patients exhibited vHITs with refixation saccades but normal gain. Saccades mostly occurred bilaterally. There was no correlation between vHIT gain or saccades and caloric irrigation, cervical vestibular evoked myogenic potential or audiometry for Menière's ears. Furthermore, vHIT gain or saccades correlated neither with age nor with the duration of the disease. CONCLUSIONS: Pathological low vHIT gain values are rarely observed in patients with certain Menière's disease, while refixation saccades occur very frequently. In the majority of patients, saccades occur bilaterally. In Menière's disease, in contrast to vestibular neuritis, there is no compensatory decrease of saccade latency over time.

Clinical manifestations of hydropic ear disease (Menière's).

INTRODUCTION: Hydropic ear disease, initially described by and named after Prosper Menière, is one of the most frequent vertigo disorders and one of the most frequent inner ear disorders. It is the syndrome of endolymphatic hydrops which until 2007 could be diagnostically confirmed only by post-mortem histology. In the past, various attempts to formulate clinical diagnostic criteria have been undertaken but were hampered by the inability to ascertain the diagnosis in living patients. With the milestone achievement of endolymphatic hydrops imaging, today the pathology can be ascertained. In this study, we have performed a detailed analysis of the clinical features of hydropic ear disease for the first time by examining a large cohort of patients with morphologically confirmed endolymphatic hydrops using a detailed physician-administered neurotologic face-to-face interview. RESULTS: During a hydropic vertigo attack, the patients report nausea, vomiting, sweating, urge to defecate, urge to urinate, phosphenes, headache, photophobia, phonophobia and even transient loss of consciousness. A third of the patients does not experience auditory symptoms during the vertigo attacks. Vertigo attacks last less than 20 min in more than one-fourth of the patients. Audiometric hearing loss has its greatest diagnostic value at the frequencies of 1 kHz and below. Cochleovestibular symptom onset simultaneity is associated with a high frequency of drop-attacks. Migraine and autoimmune disorders are not associated with hydropic ear disease. CONCLUSION: This study marks the beginning of the clinical characterization of hydropic ear disease. The findings have important implications for the future formulation of clinical diagnostic criteria.

Amiodarone: A Newly Discovered Association with Bilateral Vestibulopathy.

BACKGROUND: Bilateral vestibulopathy (BVP) is a debilitating disorder characterized by the hypofunction of both vestibular end organs or nerves. The most frequent identifiable causes of BVP are ototoxic drug effects, infectious and autoimmune disorders. However, the majority of cases remain idiopathic. Very recently, the first discovery of a clinical case of Amiodarone-associated BVP has been reported. METHODS: An overview of the literature concerning the relation between amiodarone toxicity and BVP is presented and discussed. RESULTS: Older reports on amiodarone-induced symptoms of vertigo and gait instability lack a description of vestibular function test results. Recent evidence from retrospective studies including vestibular function testing in patients taking amiodarone have identified the drug as the hitherto unsuspected potential cause of a relatively large proportion of cases with "idiopathic" BVP. CONCLUSION: Patients who receive amiodarone should be monitored with vestibular function testing in order to recognize potential adverse effects on the vestibular system and allow for an informed decision on possible drug reduction or withdrawal.

In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Menière's Disease Ears and Normal Hearing Ears.

Analysis of neural structures in Menière's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this patient group but has yet to be confirmed. This protocol describes a method of in vivo evaluation of neural changes especially well suitable for cranial nerve analysis using magnetic resonance imaging (MRI). MD-patients and normal hearing persons were examined in a 3-T MR-scanner using a scan protocol including strongly T2-weighted 3D gradient-echo-sequence (3D-CISS). In the patient group, MD was additionally confirmed using MRI-based assessment of endolymphatic hydrops. Morphometric analysis was performed using a freeware DICOM viewer. Evaluation of cranial nerves included measurements of cross-sectional areas (CSAs) of the nerves at different levels as well as orthogonal diametric measurements.

Cochlear Implant Surgery and the Risk of Falls in an Adult Population.

OBJECTIVE: To determine the effect of cochlear implant surgery on the balance and risk of falls in an adult patient population using a mobile posturograph. DESIGN: Prospective clinical pilot study. SETTING: Cochlear implant center at a tertiary referral hospital. SUBJECTS AND METHODS: Twenty adult patients undergoing cochlear implant surgery were tested using a mobile posturograph (VertiGuard). The standard balancing deficit test, or the geriatric standard balancing deficit test protocol (for patients older than 60 yr), was performed both 1 day before and 3 to 5 days after surgery. OUTCOME MEASURES: The risk of falls (%) was calculated from the body sway both forward-to-backward and side-to-side in degrees per second. RESULTS: The mean preoperative risk of falls in the whole study population was 51% (24-max. 86%) and was thus already higher than that in a normal healthy population (norm 0-40%). Comparison of the postoperative risk of falls to the preoperative risk for all 20 patients revealed a mean increased risk of falls of 1.25% after CI surgery. This is not a statistically significant increase. There was also no statistically significant increase when comparing the fall risk calculated using either the standard balancing deficit test protocol or the geriatric standard balancing deficit test protocol alone. CONCLUSION: Postural control in cochlear implant candidates is already decreased before surgery compared with a healthy population. However Comparison of pre- and postoperative body sway measurements did not reveal a significant increase in fall risk as a result of cochlea implant surgery. Therefore in this study population, cochlear implant surgery did not influence balance and risk of falls. Further testing with a larger study population would be necessary to determine the development of falls risk over time after cochlear implant surgery.

Relationship Between the Extent of Endolymphatic Hydrops and the Severity and Fluctuation of Audiovestibular Symptoms in Patients With Menière's Disease and MRI Evidence of Hydrops.

OBJECTIVE: To characterize the short-, middle-, and long-term occurrence of vertigo attacks in a large population of Menière's disease (MD) and to investigate the relationship between the extent of endolymphatic hydrops (ELH) and the severity of audiovestibular symptoms. STUDY DESIGN: Prospective observational study. METHODS: One hundred ninety-two patients with clinically definite MD participated in this study. The degree of ELH was visualized by locally enhanced inner ear magnetic resonance imaging. The occurrence and intensity of vertigo attacks, hearing loss, tinnitus, and aural fullness were documented in patient diaries. RESULTS: There was no significant correlation between the extent of cochlear or vestibular hydrops and the number of definite vertigo days, neither with regard to a short-term nor with regard to a middle-term time period. There was also no correlation between the extent of ELH and the intensity or activity of the coexisting aural symptoms hearing loss, tinnitus, and aural fullness. The duration of the disease significantly correlated with the extent of both cochlear and vestibular hydrops, but not with the number of definite vertigo days. CONCLUSION: The ELH was progressive in the long-term course of the disease in this large population of definite MD patients, but short-term and middle-term fluctuations of the symptom severity did not involve measurable variations of the ELH. Furthermore, the symptom severity did not decrease with increasing disease duration.