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).

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).

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

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

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.

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.

Amiodarone-associated 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. The majority of cases, however, remain idiopathic. METHODS: Medical records of patients diagnosed with idiopathic BVP were examined in five dizziness clinics. RESULTS: We identified 126 patients with "idiopathic" BVP. Out of these, 15 patients had a history of Amiodarone treatment before the diagnosis of BVP, resulting in a 12% prevalence. CONCLUSION: The present report supports the hypothesis that Amiodarone can cause BVP. Vestibular examination in patients taking Amiodarone and suffering from balance-related symptoms are recommended, to recognize this adverse effect as early as possible and allow for an informed judgement on a potential dose reduction or withdrawal for recovery of the vestibular function.

Morphometric evaluation of facial and vestibulocochlear nerves using magnetic resonance imaging: comparison of Menière's disease ears with normal hearing ears.

Loss of neural structures (such as hair cells or neurones within the spiral ganglion) has been proposed to be involved in Menière's disease (MD) (Spoendlin et al. Acta oto-laryngologica Supplementum 499:1-21, 1; Merchant et al. Eur Arch Oto-Rhino-Laryngol Off J Eur Feder Oto-Rhino-Laryngol Soc (EUFOS) Affil German Soc Oto-Rhino-Laryngol Head Neck Surg 252(2):63-75, 2; Tsuji et al. Ann Otol Rhinol Laryngol Suppl 81:26-31, 3; Kariya, Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 28(8):1063-1068, 4; Megerian Laryngoscope 115(9):1525-1535, 5) but this has yet to be confirmed. Therefore, the aim of this study was to investigate morphometric changes of VIIth and VIIIth cranial nerve in MD. MD is characterized by episodic vertigo, tinnitus, fluctuating hearing loss, and aural fullness. The exact pathophysiological mechanisms involved such as viral infections, autoimmune processes, genetic predisposition, cellular apoptosis, and oxidative stress are still not clear. Using a T2-weighted 3D-GE "constructive interference in steady state" (CISS) 3T magnetic resonance imaging (MRI) sequence, we evaluated the properties of the VIIth and VIIIth cranial nerves as they passed from the cerebellopontine angle to the inner ear modiolus. 21 patients with MD were examined along with 39 normal controls. Bidirectional nerve diameters and cross-sectional areas (CSA) were measured in a transverse plane. The comparison of study and control group showed statistically significant (P < 0.000595 after Bonferroni correction) differences between the CSA measurements. The facial, cochlear, superior vestibular, and inferior vestibular nerves (FN, CN, SVN, IVN) of MD patients were significantly larger than those of the control group, both on the MD-affected side and on the healthy side. Thus for example, the cochlear nerve CSA measurements were 0.69 ± 0.14 mm2 (P < 0.0001) in the affected ears of the unilateral MD group, 0.70 ± 0.12 mm2 (P < 0.0001) in the affected ears of the cohort including the bilateral MD group, 0.71 ± 0.13 mm2 (P < 0.0001) in the non-affected ears of the MD patients, as compared to 0.46 ± 0.14 mm2 in the control group. The perpendicular nerve diameters were found to vary according to site of measurement and type of measurement used. For example a statistically significant enlargement of the short diameter measurements of the SVN at the level of the meatus was found, but not of long diameter measurements at the same site. Although cellular death would theoretically be expected to lead to a decreased nerve thickness, our data showed a swelling of cranial nerves VII and VIII within the study group compared to our normal hearing control group. The similar reaction of the facial nerve supports mediator-based theories of MD pathophysiology.

Utilisation of multi-frequency VEMPs improves diagnostic accuracy for Meniere's disease.

To determine whether vestibular evoked myogenic potential (VEMP) measurements that combine the VEMP 500/1000 Hz frequency tuning ratio and the inter-aural asymmetry ratio can reliably detect unilateral Meniere's disease ears as compared to healthy controls. Forty-two consecutive patients with certain unilateral Meniere's disease (as confirmed using a locally enhanced inner ear MRI (LEIM)) were assessed. Cervical vestibular evoked myogenic potentials (cVEMP) and ocular vestibular evoked myogenic potentials (oVEMP) were recorded at 500 and 1000 Hz. The VEMP amplitudes, asymmetry ratios, and the 500/1000 Hz amplitude ratios were compared with those of 21 age-matched healthy controls. A multi-frequency VEMPs score that combined: (1) the cVEMP 500/1000 Hz amplitude ratio, (2) the oVEMP 500/1000 Hz amplitude ratio, (3) the 500 Hz cVEMP asymmetry ratio, (4) the 1000 Hz cVEMP asymmetry ratio, produced a ROC curve with an area under the curve (AUC) of 0.814. The inclusion of audiology data further improved the result to 0.906. This score can be used to discriminate with a good degree of clinical accuracy between Meniere's ears (unilateral) and those of healthy controls. Multi-frequency VEMP analysis offers a simple, cost-effective solution to the diagnostic difficulties presented by Meniere's disease.

Audiovestibular Function Deficits in Vestibular Schwannoma.

Introduction. Vestibular schwannomas (VS) are benign tumours of the vestibular nerve and can lead to hearing loss, tinnitus, vertigo, facial palsy, and brainstem compression. Audiovestibular diagnostic tests are essential for detection and treatment planning. Methods. Medline was used to perform a systematic literature review with regard to how audiovestibular test parameters correlate with symptoms, tumour size, and tumour location. Results. The auditory brainstem response can be used to diagnose retrocochlear lesions caused by VS. Since hearing loss correlates poorly with tumour size, a retrocochlear lesion is probably not the only cause for hearing loss. Also cochlear mechanisms seem to play a role. This can be revealed by abnormal otoacoustic emissions, despite normal ABR and new MRI techniques which have demonstrated endolymphatic hydrops of the inner ear. Caloric and head impulse tests show frequency specific dynamics and vestibular evoked myogenic potentials may help to identify the location of the tumour regarding the involved nerve parts. Conclusion. In order to preserve audiovestibular function in VS, it is important to stop the growth of the tumour and to avoid degenerative changes in the inner ear. A detailed neurotological workup helps to diagnose VS of all sizes and can also provide useful prognostic information.

Enhancing the reproducibility of ocular vestibular evoked myogenic potentials by use of a visual target originating from a head-mounted laser.

Ocular vestibular evoked myogenic potentials (oVEMPs) represent extraocular muscle activity in response to vestibular stimulation. oVEMP amplitudes are known to increase with increasing upward gaze angle, while the patient fixates a visual target. We investigated two different methods of presenting a visual target during oVEMP recordings. 57 healthy subjects were enrolled in this study. oVEMPs were elicited by 500 Hz air-conducted tone bursts while the subjects were looking upward at a marking which was either fixed on the wall or originated from a head-mounted laser attached to a headband, in either case corresponding to a 35° upward gaze angle. oVEMP amplitudes and latencies did not differ between the subjects looking at the fixed marking and the ones looking at the laser marking. The intra-individual standard deviation of amplitudes obtained by two separate measurements for each subject, however, as a measure of test-retest reliability, was significantly smaller for the laser headband group (0.60) in comparison to the group looking at the fixed marking (0.96; p = 0.007). The intraclass correlation coefficient revealed better test-retest reliability for oVEMP amplitudes when using the laser headband (0.957) than using the fixed marking (0.908). Hence, the use of a visual target originating from a headband enhances the reproducibility of oVEMPs. This might be due to the fact that the laser headband ensures a constant gaze angle and rules out the influence of small involuntary head movements on the gaze angle.

Monitoring parotid gland tumors with a new perfusion software for contrast-enhanced ultrasound.

PURPOSE: Contrast enhanced ultrasound (CE-US) is a promising imaging modality for non-invasive analysis of functional vascularisation. Lesions of the parotid gland are associated with a vascularisation that differs from normal gland tissue. The aim of this clinical study was to further analyse the perfusion in parotid gland lesions with CE-US. The new quantification software VueBox (Bracco, Italy) was used to assess the perfusion, based on DICOM datasets of CE-US examination. MATERIALS AND METHODS: CE-US measurements were performed by intravenous application of a contrast agent (SonoVue, Bracco, Italy) before surgical tumor resection. From the analysis of a time sequence of 2D DICOM contrast images, area under time intensity curve (AUC), peak enhancement (PE), wash-in-rate (WiR) and wash-in-perfusion-index (WiPI) were calculated using VueBox. These were correlated with the histological analyses of the tumor tissue. RESULTS: Significant difference of area below intensity time curve (AUC), peak enhancement (PE), wash-in-rate (WiR) and wash-in perfusion index (WiPI) were observed in the malign lesions compared to benign tumors (p < 0,05) and in pleomorphic adenoma compared to cystadenolymphoma (p < 0,05). CONCLUSION: CE-US seems to be a quantitative and independent method for discriminating between malign and benign parotid gland tumors.

Dynamic contrast-enhanced ultrasound for differential diagnosis of submandibular gland disease.

Intensity-time gradients (ITGs) of contrast-enhanced ultrasound (CEUS) can be used for non-invasive monitoring of gland-preserving treatment effects in sialolithiasis-related chronic sialadenitis as well as for imaging vascularization in tumors. The aim of this clinical trial was to evaluate feasibility to distinguish different entities of submandibular gland disease including inflammatory alterations of the submandibular gland as well as benign and malignant tumors. In this prospective clinical study, ITGs in 30 patients with sialolithiasis-related chronic sialadenitis or an unilateral submandibular mass and 18 disease-free submandibular gland controls were quantitatively analyzed by CEUS using the contrast agent SonoVue. In addition, clinical complaints according to visual analog scales (VAS) were documented. VAS data documented significantly less complaints only in benign tumors compared with the other pathologies of the submandibular gland. In parallel, CEUS-derived ITGs revealed significantly reduced ITGs only in benign tumors (n = 5) compared to the controls (n = 18). Despite of comparably reduced wash-in velocities in malignant lesions (n = 3) statistical significance was not reached. Chronic sialadenitis (n = 18) and its sclerosing variant (Küttner tumor, n = 4) revealed comparable ITGs as controls. Tumors of the submandibular gland present with reduced functional microcirculatory networks comparing with healthy gland controls and chronically inflamed submandibular glands. Thus, dynamic CEUS-derived ITGs in combination with conventional clinical measures--for example VAS--appear as a safe and promising strategy for non-invasive diagnostic workup of submandibular lesions and warrant further validation in a larger set of patients.

The effects of rise/fall time and plateau time on ocular vestibular evoked myogenic potentials.

Ocular vestibular evoked myogenic potentials (oVEMP) are strongly influenced by recording conditions and stimulus parameters. Throughout the published literature, a large variety of stimuli is used for eliciting oVEMP. Our objective was to determine the effects of different rise/fall times and plateau times on oVEMP amplitudes and latencies. 32 healthy subjects were enrolled in the study. 500 Hz air-conducted tone bursts with the parameters rise-plateau-fall time 0-4-0, 4-0-4, 2-2-2 and 2-4-2 ms were used for eliciting oVEMP. For all stimuli, response prevalences were 100 %. The 4-0-4 ms stimulus generated the smallest amplitudes, whereas the 2-2-2 and 0-4-0 ms stimuli achieved the largest amplitudes. n1 and p1 latencies were significantly shorter for the 0-4-0 ms than for the other stimuli, whereas latencies in response to the 4-0-4 ms stimulus were prolonged. Hence, a variety of stimuli is suitable for evoking oVEMP in healthy subjects. We recommend a 2-2-2 ms stimulus for clinical testing of oVEMP elicited by air conducted sound, because it reproducibly generates oVEMP without exposing the ear to unnecessary amounts of acoustic energy.

Endolymphatic hydrops in patients with vestibular migraine and auditory symptoms.

Vertigo patients exhibiting features of vestibular migraine (VM) and Menière's disease (MD) present a difficult diagnostic challenge to the clinician, and the two entities are likely to overlap. The aim of the present study was to investigate the occurrence of endolymphatic hydrops in patients with VM and auditory symptoms. This was an observatory diagnostic study. At an academic interdisciplinary dizziness centre, nineteen consecutive patients with definite or probable VM and auditory symptoms were examined by locally enhanced inner ear MR imaging. MR images were evaluated for the presence of endolymphatic hydrops. Of the 19 included patients, four patients (21 %) demonstrated evidence of cochlear and vestibular endolymphatic hydrops on locally enhanced inner ear MR imaging (three with "definite VM", one with "probable VM"). Locally enhanced inner ear MR imaging may be useful in the diagnostic evaluation of patients with VM and auditory symptoms, as some of these patients have signs of endolymphatic hydrops. Whether these patients suffer from MD only and are misdiagnosed as VM or suffer from both, VM and MD or whether endolymphatic hydrops is a consequence of inner ear damage due to VM are clinically relevant questions that can be evaluated by application of this technique.

Perfusion characteristics of parotid gland tumors evaluated by contrast-enhanced ultrasound.

PURPOSE: Contrast enhanced ultrasound (CE-US) is a promising imaging modality for non-invasive analysis of parotid gland lesions because their vascularisation differs from normal gland tissue. This clinical study should further investigate CE-US as a diagnostic tool for parotid gland tumors. MATERIALS AND METHODS: 39 patients underwent CE-US measurements after intravenous application of a contrast agent (SonoVue, Bracco, Italy) before surgical tumor resection. Time-intensity curves gradients were calculated and parameters of intratumoral microcirculation were analysed. The vascularisation parameters were compared among the different tumor entities as defined per definitive histological diagnosis. RESULTS: Histological analyses revealed 17 pleomorphic adenoma, 15 cystadenolymphoma and 7 malignoma. A significant difference of area below intensity time curve (AUC) and mean transit time (MTT) was measured in the malignant lesions compared to benign tumors (p<0.05). A significant difference of AUC and maximum of signal increase (ΔSImax) for pleomorphic adenoma versus cystadenolymphoma was found (p<0.05). CONCLUSION: CE-US seems to be a quantitative and independent method for the assessment of malign and benign parotid gland tumors. Further studies and clinical experience will have to validate this method as a reliable diagnostic tool that facilitates preoperative planning.