Untargeted Metabolomic Analysis in Endolymphatic Sac Luminal Fluid from Patients with Meniere’s Disease

Journal of the Association for Research in Otolaryngology - Dysfunction of the endolymphatic sac (ES) is one of the etiologies of Meniere’s disease (MD), the mechanism of which remains...     

Endolymphatic hydrops in patients with unilateral and bilateral Meniere’s disease

Conclusion: All definite Meniere’s disease (MD) had endolymphatic hydrops (EH) at least in the cochlea or the vestibule. Symptoms of MD may appear after formation of EH. It is assumed that the probability of immediate progression to bilateral MD from unilateral MD is very low in patients without EH on the non-affected side.

Objective: To evaluate the EH on both sides in patients with unilateral and bilateral MD, and to investigate factors with progression to bilateral MD including the degree of EH, hearing level, and the duration of MD.

Patients and methods: The study included 29 patients with unilateral definite MD and 12 patients with bilateral definite MD. The endolymphatic space size was visualized by using 3-Tesla magnetic resonance imaging.

Results: All patients with unilateral and bilateral MD had significant or mild EH at least in the cochlea or the vestibule on the affected side. On the non-affected side, EH was not observed at all in eight patients, but asymptomatic EH was observed in the cochlea in 14 patients and in the vestibule in 16 patients. There was no relationship between the EH on the non-affected side and the duration of MD.     

Endolymphatic space size in patients with Meniere’s disease and healthy controls

Conclusions: The incident ratios of cochlear and/or vestibular endolymphatic hydrops (EH) were significantly higher in the affected ears of patients with Meniere’s disease (MD) than in the ears of healthy controls. There were no significant differences between controls and the contralateral ears of MDs. Objectives: The aim was to compare the incidence ratios of EH between unilateral/bilateral MD and controls using 3T magnetic resonance imaging (MRI) with intravenous gadolinium. Methods: A total of 41 patients were diagnosed with MD: 32 with unilateral MD (uMD) and nine with bilateral MD (bMD). Fifteen healthy volunteers were enrolled as controls. The patients underwent 3T MRI 4?h after intravenous injection of gadolinium. Results: Cochlear EH was present in 3.3% of 30 ears of 15 controls, 6.3% of 32 contralateral (contra) ears of 32 uMDs, 62.5% of 32 affected ears of 32 uMDs, and 55.6% of 18 affected ears of nine bMDs. Vestibular EH was observed in 6.7% of control ears, 3.1% of contra-uMD ears, 65.6% of affected uMD ears, and in 55.6% of affected bMD ears. Either cochlear or vestibular EH was present in 10.0% of control ears, 6.3% of contra-uMD ears, 81.3% of affected uMD ears, and 44.4% of affected bMD ears.     

Enhanced Vestibulo-ocular Reflex to Electrical Vestibular Stimulation in Meniere’s Disease

Meniere’s disease is characterized by sporadic episodes of vertigo, nystagmus, fluctuating sensorineural hearing loss, tinnitus and aural pressure. Since Meniere’s disease can affect different regions of the vestibular labyrinth, we investigated if electrical vestibular stimulation (EVS) which excites the entire vestibular labyrinth may be useful to reveal patchy endorgan pathology. We recorded three-dimensional electrically evoked vestibulo-ocular reflex (eVOR) to transient EVS using bilateral, bipolar 100-ms current steps at intensities of 0.9, 2.5, 5.0, 7.5 and 10.0 mA with dual-search coils in 12 unilateral Meniere’s patients. Their results were compared to 17 normal subjects. Normal eVOR had tonic and phasic spatiotemporal properties best described by the torsional component, which was four times larger than horizontal and vertical components. At EVS onset and offset of 8.9 ms latency, there were phasic eVOR initiation (M = 1,267 °/s²) and cessation (M = −1,675 °/s²) acceleration pulses, whereas during the constant portion of the EVS, there was a maintained tonic eVOR (M = 9.1 °/s) at 10 mA. However in Meniere’s disease, whilst latency of EVS onset and offset was normal at 9.0 ms, phasic eVOR initiation (M = 1,720 °/s²) and cessation (M = −2,523 °/s²) were enlarged at 10 mA. The initiation profile was a bimodal response, whilst the cessation profile frequently did not return to baseline. The tonic eVOR (M = 20.5 °/s) exhibited a ramped enhancement of about twice normal at 10 mA. Tonic eVOR enhancement was present for EVS >0.9 mA and disproportionately enhanced the torsional, vertical and horizontal components. These eVOR abnormalities may be a diagnostic indicator of Meniere’s disease and may explain the vertigo attacks in the presence of declining mechanically evoked vestibular responses.     

Evidence of surgical treatments for intractable Meniere’s disease

Meniere’s disease is an inner ear disease, characterized by recurrent rotatory vertigo, sensorineural hearing loss and tinnitus. There are some with frequent vertigo attacks, progressive hearing loss and persistent annoying tinnitus even through the continuous standard medical treatments. These cases are thought to account for 10%–20% of all cases of Meniere’s disease. In this review article, we would like to demonstrate the evidences for surgical treatments according to the previous papers, and consider the next therapeutic strategies including surgical options according to the international guidelines.     

Current state of evidence for endolymphatic sac surgery in Menière’s disease: a systematic review

Abstract

Background: Endolymphatic sac surgery is an invasive procedure recommended to patients with Menière’s disease.

Aims/Objectives: To provide an overview and quality assessment of the existing evidence and to provide an updated assessment of the utility of endolymphatic sac surgery in Menière’s disease.

Material and Methods: We performed a systematic literature search for systematic reviews and randomized controlled trials (RCTs). The AMSTAR tool was used to assess the quality of systematic reviews and the Cochrane risk of bias tool for RCTs. The overall certainty of effects for the individual outcomes was evaluated using the GRADE approach.

Results: One systematic review of high quality matched the inclusion criteria, and included three RCTs. An updated literature search from the last search date of the included review provided no further relevant RCTs. The identified RCTs individually reported a positive effect of both the placebo and active treatment groups following surgery, strongly indicative of a placebo effect. The overall certainty of the effect was very low.

Conclusions and significance: There is still a lack of high-quality research suggesting that endolymphatic sac surgery provides a significant amount of symptomatic relief for Menière’s patients.     

Practical 3DCT imaging of the vestibular aqueduct for Meniere’s disease

Conclusion: Radiographic visualization of the vestibular aqueduct (VA) from a lateral inside view was effective in assessing patients with Meniere’s disease (MD). There were no VA shapes specific to MD on radiography, except for an obliterated VA. This technique could yield more accurate images and functional assessment of the VA for MD evaluation in a clinically useful and convenient manner, without requiring morphologic measurement. Objective: To visualize the detailed images of the VA using three-dimensional (3D) computed tomography (CT) and discuss its clinical utility in assessing MD. Subjects and methods: The VAs in 13 healthy subjects and 25 MD patients, who were definitely diagnosed according to criteria described by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology, Head and Neck Surgery (AAO-HNS), were imaged from the medial and lateral sides using 3DCT and compared to conventional CT images. Results: Examination of the VA from both the lateral outside and inside views on 3DCT yielded more precise images than generated by conventional CT and could be useful to estimate the VA function. The estimated VA function in the MD ears was significantly abnormal compared to the function in healthy ears. An obliterated VA was characteristic of affected MD ears.     

Therapeutic role of intravenous glycerol for Meniere’s disease. Preliminary results

PurposeOsmotic diuretics such as glycerol are used for diagnostic purposes in patients with a suspect of Meniere's disease (MD). Scientific evidence in the animal model and in humans has shown that glycerol can induce a reduction in endolymphatic hydrops; however, its use for therapeutic purposes in MD has never been reported. The aim of this study was to evaluate the effectiveness on symptom control of intravenous glycerol in a sample of patients with definite unilateral MD not responsive to dietary restrictions.Materials and methodsForty patients with unilateral intractable MD were included in the study. After audio-vestibular evaluation, patients were treated with intravenous 10% glycerol with 0.9% sodium chloride, 0.5 g/kg ml once a day for 2 consecutive days every fifteen days for six months. Vertigo attacks were evaluated before and after therapy and categorized into classes A–F according to the 2015 Equilibrium Committee criteria. Tinnitus and quality of life were evaluated through the Tinnitus Handicap Inventory and the Functionality Level Scale questionnaires.ResultsBefore treatment, patients had an average of 3.2 vertigo attacks/month; during the six months after treatment the average number of attacks/month decreased to 1.2 (p < 0.0001). At the end of the study period, 25 patients (62.5%) were in Class B vertigo control; 10 patients (25%) in Class C; and 5 patients (12.5%) in Class D. No patients were in Class A, E and F. No hearing deterioration was found in all treated patients. Quality of life according to administered questionnaires improved after treatment.ConclusionsIn our sample, intravenous infusion of glycerol for two consecutive days every fifteen days for six months based on the patient's weight improved vertigo attacks and reduced the discomfort generated by tinnitus raising quality of life in patients with unilateral MD unresponsive to dietary restrictions.     

Effects of posterior tympanotomy with steroids at round window on hearing recovery after revision surgery for intractable Meniere’s disease

Conclusions: At the second postoperative year, there were no significant differences between results for vertigo and hearing after endolymphatic sac drainage with steroid instillation surgery (EDSS) and EDSS with posterior tympanotomy with steroids at the round window (EDRW). In particular, as regards hearing recovery to the preoperative level, the periods after EDRW were shorter than those after the second EDSS. Objectives: Patients sometimes faces recurrent problems years after EDSS due to endolymphatic sac closure and/or disease progression. In the present study, we examined the effects of EDRW on vertigo and hearing after revision surgery for intractable relapsed Meniere’s disease. Methods: Sixteen patients with Meniere’s disease had revision surgery due to intractable recurrence of disease, and were followed up regularly at least for 2 years. As revision surgery, EDSS was performed repeated in eight cases and EDRW was performed in the other eight. There were no significant differences between the patients’ backgrounds in the two groups. Results: Periods of hearing recovery to the preoperative level were 11.5 ± 4.4 months after the first EDSS, although it took 16.4 ± 2.6 months longer after revision surgery with the second EDSS (p = 0.038 < 0.05: first EDSS vs second EDSS) and was 10.0 ± 3.3 months shorter after revision surgery with EDRW (p = 0.010 < 0.05: second EDSS vs EDRW).     

Meniere’s,migraine, and motion sickness

Conclusion: Elevated Motion Sickness Susceptibility (MSS) in Meniere?s disease (MD) is likely to be a consequence of the onset of MD and not migraine per se.

Objectives: Pathologies of the vestibular system influence MSS. Bilateral vestibular deficits lower MSS, vestibular neuritis or benign paroxysmal positional vertigo have little overall effect, whereas vestibular migraine elevates MSS. However, less is known about MSS in MD, a condition in which many patients experience vestibular loss and migraine symptoms.

Methods: The authors conducted an online survey that posed diagnostic and disease questions before addressing frequency of headaches, migraines, visual display dizziness (VDD), syncope, social life, and work impact of dizziness (SWID4) and motion sickness susceptibility (MSSQ). The two groups were: diagnosed MD individuals with hearing loss (n?=?751) and non-MD individuals in the control group (n?=?400).

Results: The MD group showed significantly elevated MSS, more headache and migraine, increased VDD, higher SWID4 scores, and increased syncope. MSS was higher in MD than controls only after the development of MD, but not before, nor in childhood. Although elevated in MD compared with controls, MSS was lower than migraine patients from past data. Multivariate analysis revealed VDD, SWID4, and MSS in adulthood as the strongest predictors of MD, but not headache nor migraine.     

Repeated courses of intratympanic dexamethasone injection are effective for intractable Meniere’s disease

Conclusion: Intra-tympanic dexamethasone injection (ITD) could serve as a first-line intra-tympanic (IT) treatment for Meniere’s disease (MD), regardless of hearing level. Even if the response to initial ITD course was unsatisfactory, a repeated course may be beneficial with some patients.

Objectives: This study examined the effect of repeated courses of ITD administered on demand and investigated the possibility of ITD as an initial IT treatment for medically intractable MD patients.

Method: Fifty-one patients who had been diagnosed with definite MD and given course(s) of ITD treatment were included. Vertigo control, pure tone average and functional disability scores were evaluated against the American Academy of Otolaryngology-Head and Neck Surgery guidelines for MD.

Results: Vertigo disappeared or was substantially controlled in 58.8% and 23.5% of the patients, respectively, after the first ITD course. A repeated course further raised the complete vertigo control rate by 15.7% and intra-tympanic gentamycin injection could be postponed or avoided in 78.6% of the patients who required repeated IT treatment. Hearing was unchanged after the first course of ITD (p?>?.05). No significant differences were detected in the clinical profiles or laboratory findings between patients receiving single course of ITD and those on multiple courses (p?>?.05).