Inter-frequency amplitude ratio of oVEMP for differentiating Meniere's disease from BPPV: clinical validation using a double-blind approach.

OBJECTIVE: The study aimed at examining the usefulness of inter-frequency amplitude ratio (IFAR) of ocular vestibular evoked myogenic potential (oVEMP) in identifying Meniere's disease (MD) and differentiating it from benign paroxysmal positional vertigo (BPPV). DESIGN: A case-control design was used with a double blind approach. Phase 1 included 70 healthy individuals and 36 individuals each with MD and BPPV and Phase 2 included 20 individuals each with MD and BPPV. The age range of the participants in both phases was 15-50 years. All participants underwent oVEMP testing using 500 and 1000 Hz tone bursts and IFAR was obtained. RESULTS: The results in phase 1 revealed significantly higher IFARs in Meniere's disease than BPPV and healthy individuals (p < 0.001). An optimum criterion point of IFAR ≥1.11 for diagnosing MD was found which yielded 80% sensitivity and 98% specificity. The results in phase 2 demonstrated 85% correct identification of MD and 95% correct rejection of BPPV as non-MD. CONCLUSIONS: IFAR of oVEMP appears highly sensitive and specific parameter for identifying MD and a clinically valid tool for differentiating MD from BPPV.

Characterizing the Age and Stimulus Frequency Interaction for Ocular Vestibular-Evoked Myogenic Potentials.

OBJECTIVES: The normal process of aging is mostly associated with global decline in almost all sensory aspects of the human body. While aging affects the 500-Hz tone burst-evoked ocular vestibular-evoked myogenic potentials (oVEMPs) by reducing the amplitudes and prolonging the latencies, its interaction with oVEMP responses at other frequencies has not been studied. Therefore, the present study aimed at investigating the impact of advancing age on the frequency tuning of oVEMP. DESIGN: Using a cross-sectional research design, oVEMPs were recorded for tone burst frequencies of 250, 500, 750, 1000, 1500, and 2000 Hz from 270 healthy individuals divided into six age groups (10-20, 20-30, 30-40, 40-50, 50-60, and >60 years). RESULTS: The results revealed significantly lower response rates and amplitudes in age groups above 50 years of age than all the other groups at nearly all the frequencies (p < 0.05). Further, the frequency tuning was obtained at 500 or 750 Hz in majority of individuals below 60 years of age and at ≥1000 Hz in most of the individuals above 60 years of age (p < 0.05). Thus, there was a significant shift in frequency tuning of oVEMP from 500 or 750 Hz in the younger and the middle-aged adults to ≥1000 Hz in older adults, especially above 60 years of age. CONCLUSIONS: The results of the study showed significantly higher prevalence of frequency tuning at 1000 Hz in older adults above 60 years of age. Because the shift in frequency tuning to ≥1000 Hz is frequently used for identification of Meniere's disease, it is suggested that age-related correction be used for the diagnosis of Meniere's disease when using frequency tuning of oVEMP.

Delayed Effect of Active Pressure Treatment on Endolymphatic Hydrops.

OBJECTIVE: To identify eventual correlations between the effect of low-pressure treatment and endolymphatic hydrops in Ménière patients. MATERIAL AND METHODS: The study group consisted of subjects affected by definite Ménière disease (2015) and a severe degree of disability, who received a ventilation tube with or without a low-pressure treatment before undergoing a surgical procedure (vestibular neurectomy). After the placement of the ventilation tube, the subjects were either left alone with the tube or received 1 month of self-administered low-pressure therapy with a portable device. In all subjects, an electrocochleography (ECochG) was performed and specific questionnaires - Dizziness Handicap Inventory (DHI) and Functional Scale Level (FSL) - were completed before starting either arm of treatment, at the end of treatment, and then 3 and 6 months later. RESULTS: All selected subjects presented with an ECochG pattern that was indicative of endolymphatic hydrops before starting either treatment. At the end of pressure treatment, 80% showed symptomatic improvement while maintaining the hydropic ECochG pattern. At the 3-month control stage, the hydropic pattern resulted normalized (<0.5) in all the improved subjects. CONCLUSIONS: Although 1 month of low-pressure treatment provided a positive symptomatological outcome, normalization of the hydropic ECochG parameters occurred only at a later time. Therefore, it is possible to assume that endolymphatic hydrops could be concurrent with a non-symptomatic stage of Ménière disease, and that the anti-hydropic effect of the low-pressure treatment, if any, would present with a certain delay after its completion.

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.

Diagnostic value of vestibular-evoked myogenic potentials in Ménière's disease and vestibular migraine.

Overlaps can be seen between vestibular migraine (VM) Ménière's Disease (MD) and diagnosis is difficult if hearing is normal. We aimed to investigate the sacculo-collic pathway in VM patients, MD patients, and healthy controls to define the diagnostic role of cervical VEMP (cVEMP). VEMP testing in response to 500 Hz and 1000 Hz air-conducted tone burst (TB) stimulation was studied prospectively in 22 subjects with definite VM (according to Bárány nomenclature), 30 subjects with unilateral definite MD, and 18 volunteers matched healthy controls. In VM subjects, response rate, p13 and n23 latencies were similar to healthy controls, but peak-to-peak amplitudes were bilaterally reduced at 500 Hz TBs (p= 0.005). cVEMP differentiated MD patients from VM and healthy controls with asymmetrically reduced amplitudes on affected ears with low response rates at 500 Hz TBs, and alteration of frequency dependent responses at 500 and 1000 Hz TBs. These findings suggest that cVEMP can be used as a diagnostic test to differentiate MD from VM. On the other hand, VEMP responses are symmetrically reduced on both sides in VM patients, suggesting that otolith organs might be affected by migraine-induced ischemia.

Abnormal fast fluctuations of electrocochleography and otoacoustic emissions in Menière's disease.

The responses of cochlear hair cells to sound stimuli depend on the resting position of their stereocilia bundles, which is sensitive to the chemical and mechanical environment. Cochlear hydrops, a hallmark of Menière's disease (MD), which is likely to come with disruption of this environment, results in hearing symptoms and electrophysiological signs, such as excessive changes in the cochlear summating potential (SP) and in the postural shifts of distortion-product otoacoustic emissions (DPOAEs). Here, SP from the basal part of the cochlea and DPOAEs from the apical part of the cochlea were recorded concomitantly in 73 patients with a definite MD, near an attack (n = 40) or between attacks with no clinical symptoms (n = 33), to compare their sensitivities to posture and evaluate their stability. The phase of the 2f1-f2 DPOAEs was monitored during body tilt, with stimuli f1 = 1 kHz and f2 = 1.2 kHz at 72 dB SPL. Extratympanic electrocochleography was performed in response to 95-dBnHL clicks. The normal limits of the DPOAE phase shift with body tilt, [-18°, +38°], and of the SP to action-potential (AP) ratio, <0.40, were exceeded in 75% and 60% of patients, respectively, near an attack. In these patients, but not in the asymptomatic ones, both tests reveal fluctuating cochlear responses from one data sample to the next. They emphasize how hydrops hinders normal hair-cell operation and may generate fast fluctuations in inner-ear functioning. If these fluctuations also occur on shorter time scales, it might explain the imperfect diagnostic sensitivity of SP and DPOAE tests, as averaging procedures would tend to level out transient fluctuations characteristic of hydrops.

Diagnostic value of frequency-associated vestibular-evoked myogenic potential responses in Ménière's disease.

Thirty subjects with unilateral Ménière's disease (MD) and 18 age-matched controls underwent cervical (cVEMP) and ocular vestibular-evoked myogenic potential (oVEMP) testing using bilateral air-conducted stimulation (ACS) with stimulus frequencies of 500 and 1,000 Hz. The aim of this study is to determine the diagnostic value of frequency-associated responses in MD using oVEMP and cVEMP following 500- and 1,000-Hz ACS. In healthy controls and unaffected ears, responses to 500 Hz were found better than 1,000-Hz ACS in both oVEMP and cVEMP, while ears with MD responded to 1,000-Hz ACS better than to 500-Hz ACS in oVEMP. In cVEMP tests, affected ears responded to 500-Hz and 1,000-Hz ACS equally. Amplitude ratios of 1,000/500 Hz in both oVEMP and cVEMP were successful in differing affected ears from unaffected ears and healthy controls. This study showed frequency alteration of oVEMP and cVEMP can be used as a diagnostic test battery in MD.

Auto-inflammatory challenge of the endolymphatic sac--Cochlear damage measured by distortion product oto-acoustic emissions.

CONCLUSION: Twenty-five rats were challenged by an immunologic attack of the endolymphatic sac. After 6 months, distortion product oto-acoustic emissions (DPOAE) revealed a dysfunction of the outer hair cells and immunological active cells were observed in the endolymphatic sac. This information could contribute to the understanding of Ménière's disease. OBJECTIVES: This study investigated if an autoimmune challenge of the endolymphatic sac could affect DPOAE output measurements in rats. Also, a potential autoimmune cell infiltration of the endolymphatic sac was investigated. METHODS: Eighteen Lewis rats were immunized with a crude endolymphatic sac extract in complete Freund's adjuvant. Seven control animals were injected with Freund's adjuvant in saline. Cochlear damage was estimated by DPOAE dynamics 3 weeks and 6 months after the immunization. Infiltrative cells in the endolymphatic sac were investigated with transmission electron microscopy. RESULTS: The hearing assessment 6 months after immunization revealed a reduction of the DPOAE, on the full range of frequencies (2-63 kHz) in an average of the mean, of 2 dB ± 1.1 in the immunized group compared to the controls (p < 0.05). The same test showed a 2.5 dB decrease from 2 to 5 kHz (p < 0.01). Immunological active cells were observed in the endolymphatic sac in most of the immunized rats.

Hearing thresholds and FMRI of auditory cortex following eighth cranial nerve surgery.

OBJECTIVE: Determine whether auditory cortex (AC) organization changed following eighth cranial nerve surgery in adults with vestibular-cochlear nerve pathologies. We examined whether hearing thresholds before and after surgery correlated with increased ipsilateral activation of AC from the intact ear. STUDY DESIGN: During magnetic resonance imaging sessions before and 3 and 6 months after surgery, subjects listened with the intact ear to noise-like random spectrogram sounds. SETTING: Departments of Radiology and Otolaryngology of Washington University School of Medicine. SUBJECTS AND METHODS: Three patients with acoustic neuromas received Gamma Knife radiosurgery (GK); 1 patient with Meniere's disease and 5 with acoustic neuromas had surgical resections (SR); 2 of the latter also had GK. Hearing thresholds in each ear were for pure tone stimuli from 250 to 8000 Hz before and after surgery (3 and 6 months). At the same intervals, we imaged blood oxygen level-dependent responses to auditory stimulation of the intact ear using an interrupted single-event design. RESULTS: Hearing thresholds in 2 of 3 individuals treated with GK did not change. Five of 6 individuals became unilaterally deaf after SRs. Ipsilateral AC activity was present before surgery in 6 of 9 individuals with ipsilateral spatial extents greater than contralateral in 3 of 9. Greater contralateral predominance was significant especially in left compared to right ear affected individuals, including those treated by GK. CONCLUSION: Lateralization of auditory-evoked responses in AC did not change significantly after surgery possibly due to preexisting sensory loss before surgery, indicating that less than profound loss may prompt cortical reorganization.

Association between polymorphisms in genes encoding methylenetetrahydrofolate reductase and the risk of Ménière's disease.

Folate metabolism is essential for cellular functioning. Despite extensive research on the roles of folate-metabolism-related gene polymorphisms in the pathophysiology of many diseases, such as cardiovascular disease, cancers, and sudden sensorineural hearing loss, little is known about their association with Ménière's disease (MD). The aim of this study was to investigate the effect of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) on the risk of MD in a Japanese population. We examined the C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the MTHFR gene and compared them between 1946 adults (986 men and 960 women) participating in the National Institute for Longevity Sciences Longitudinal Study of Aging and 86 cases of MD. A multiple logistic regression was performed to obtain odds ratios (ORs) for the risk of MD regarding the MTHFR polymorphisms before (model 1) and after (model 2) adjustment for age and sex factors. The OR of MTHFR C677T for the risk of MD was 0.669 (95% confidence interval [CI], 0.479-0.934) in model 1 and 0.680 (95% CI, 0.484-0.954) in model 2. In contrast, the OR of MTHFR A1298C for the risk of MD was 1.503 (95% CI, 1.064-2.123) in model 1 and 1.505 (95% CI, 1.045-2.167) in model 2. Our results imply that the MTHFR C677T and A1298C polymorphisms are associated with the risk of MD.

Characteristics and clinical applications of ocular vestibular evoked myogenic potentials.

Recently, ocular vestibular evoked myogenic potentials (oVEMPs) have been described and added to the neuro-otologic test battery as a new measure for the vestibulo-ocular reflex. oVEMPs represent extraocular muscle activity in response to otolith stimulation e.g. by air-conducted sound or bone-conducted vibration. In response to vestibular stimulation, electromyographic activity of the extraocular muscles can be recorded by means of surface electrodes placed beneath the contralateral eye. oVEMPs are likely to reflect predominantly utricular function, while the widely established cervical vestibular evoked myogenic potentials (cVEMPs) assess saccular function. Thus, measuring oVEMPs and cVEMPs in addition to caloric and head impulse testing provides further evaluation of the vestibular system and enables quick and cost-effective assessment of otolith function. This review summarizes the neurophysiological properties of oVEMPs, gives recommendations for recording conditions and discusses oVEMP alterations in various disorders of the vestibular system. With increasing insight into oVEMP characteristics in vestibular disorders, e.g. Menière's disease and superior semicircular canal dehiscence syndrome, oVEMPs are becoming a promising new diagnostic tool for evaluating utricular function.

Omega-3 fatty acids: a promising possible treatment for Meniere's disease and other inner ear disorders of unknown origin?

A consolidated therapy for "idiopathic" acute disorders of the inner ear, including Meniere's Disease (MD), does not exist despite the long-lasting and widespread attempts: this lack is strictly linked to pathogenic uncertainties. According to the theoretical model that our group developed and tested over the years, a possible cause of labyrinthine damage could be identified in systemic hemodynamic changes followed by an abnormal peripheral vasoconstriction: the latter could be responsible for a more or less prolonged ischemia able to threaten a highly energy-requiring and complicated organ as the inner ear. A possible way to treat MD attacks - as well as other inner ear disorders that possibly share the same origin - according to our model should be addressed to modulate the peripheral circulation and to maintain the balance of ion exchange, acting both on systemic hemodynamics and on cell and organelle membranes. Despite the absence of such a proposal in the English literature, a reliable solution could derive from the supplementation of the intake of a nutritional principle as Omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) that seem to theoretically fulfil all the requirements necessary to achieve a homeostasis of the inner ear.

Furosemide-loading vestibular evoked myogenic potential testing can suggest developing bilateral involvement of unilateral Meniere's disease.

CONCLUSIONS: Patients with positive results of furosemide-loading vestibular evoked myogenic potential (F-VEMP) testing in the unaffected ears of unilateral Meniere's disease have a high incidence of developing bilateral lesions. OBJECTIVE: To clarify the meaning of positive results of F-VEMP testing of the unaffected ear of patients with unilateral Meniere's disease. METHODS: Twenty-five patients with unilateral Meniere's disease were investigated in this study. The positive group consisted of 6 patients with positive results of F-VEMP testing in the contralateral ear and the negative group consisted of 19 patients with negative results. The incidence of contralateral involvement was compared in both groups by the Kaplan-Meier method. RESULTS: Contralateral involvement was seen in three cases (50%) in the positive group after 2, 12, and 26 months and in three cases (16%) in the negative group after 27, 56, and 78 months. The positive group had a higher incidence of contralateral involvement than the negative group (p = 0.0017, according to a log-rank test).

Altered frequency dynamics of cervical and ocular vestibular evoked myogenic potentials in patients with Ménière's disease.

OBJECTIVE: To measure the frequency dynamics of cervical and ocular vestibular evoked myogenic potentials in healthy subjects and patients with Ménière's disease. STUDY DESIGN: A prospective cohort study. SETTING: A university teaching hospital. SUBJECTS: Eight healthy volunteers (16 ears) and 12 adult patients with unilateral Ménière's disease (8 with definite disease and 4 with probable disease) by American Academy of Otolaryngology - Head and Neck Surgery diagnostic criteria. INTERVENTIONS: Cervical and ocular vestibular evoked myogenic potentials generated by tone bursts at 250, 500, 750, 1,000, 1,500, 2,000, 3,000, and 4,000 Hz were measured in both groups. MAIN OUTCOME MEASURES: The frequency sensitivity of both the cervical and ocular vestibular evoked myogenic potentials, as evaluated by p13-n23 and n10 amplitudes in healthy ears and in ears affected and not affected by Ménière's disease. RESULTS: Cervical and ocular vestibular evoked myogenic potentials were present in all ears tested. In the healthy volunteers, the acoustic stimulus frequency at which the response amplitudes were largest was 500 Hz. This shifted to higher frequencies in patients with definite Ménière's disease for both measurements, with the effect being more pronounced for ocular vestibular evoked myogenic potentials. The shift was less marked in the probable Ménière's group and was absent in the unaffected ears of the Ménière's patients. CONCLUSION: Ménière's ears display alterations in cervical and ocular vestibular evoked myogenic potentials tuning responses with changes in the latter being more prominent. These findings indicate that the disease process affects both the otolith organs but may have an enhanced effect on the utricle. We propose that this more dominant affect may relate to the anatomical configuration of the utricle.

Ocular vestibular evoked myogenic potentials: frequency tuning to air-conducted acoustic stimuli in healthy subjects and Ménière's disease.

Ocular vestibular evoked myogenic potentials (oVEMP) in response to 250-, 500- and 1000-Hz air-conducted short tone bursts were studied in 22 healthy subjects and 37 Ménière's disease patients. The goal of this study was to investigate normal tuning characteristics of the oVEMP and the possible oVEMP changes with respect to frequency dependence in Ménière's disease. In unilateral Ménière's disease patients, a distinction was made between affected ears and unaffected ears. It was found that in normal subjects, the oVEMP tunes to a stimulus frequency of 500 Hz, with the highest amplitude and lowest threshold at this particular frequency. Generally, Ménière's disease patients showed lower amplitudes and higher thresholds than normal subjects at all 3 stimulus frequencies in both the affected and the unaffected ear. Additionally, for ears affected by Ménière's disease, the best stimulus frequency was 1000 Hz. With the use of this altered tuning for these ears, we tried to find a criterion for distinguishing normal from Ménière's disease ears.

The basis for using bone-conducted vibration or air-conducted sound to test otolithic function.

Extracellular single neuron recordings of primary vestibular neurons in Scarpa's ganglion in guinea pigs show that low-intensity 500 Hz bone-conducted vibration (BCV) or 500 Hz air-conducted sound (ACS) activate a high proportion of otolith irregular neurons from the utricular and saccular maculae but few semicircular canal neurons. In alert guinea pigs, and humans, 500 Hz BCV elicits otolith-evoked eye movements. In humans, it also elicits a myogenic potential on tensed sternocleidomastoid muscles. Although BCV and ACS activate both utricular and saccular maculae, it is possible to probe the functional status of these two sense organs separately because of their differential neural projections. Saccular neurons have a strong projection to neck muscles and a weak projection to the oculomotor system. Utricular afferents have a strong projection to eye muscles. So measuring oculomotor responses to ACS and BCV predominantly probes utricular function, while measuring neck muscle responses to these stimuli predominantly probes saccular function.

On the differential diagnosis of Ménière's disease using low-frequency acoustic biasing of the 2f1-f2 DPOAE.

We have cyclically suppressed the 2f1-f2 distortion product otoacoustic emission (DPOAE) with low-frequency tones (17-97 Hz) as a way of differentially diagnosing the endolymphatic hydrops assumed to be associated with Ménière's syndrome. Round-window electrocochleography (ECochG) was performed in subjects with sensorineural hearing loss (SNHL) on the day of DPOAE testing, and from which the amplitude of the summating potential (SP) was measured, to support the diagnosis of Ménière's syndrome based on symptoms. To summarize and compare the cyclic patterns of DPOAE modulation in these groups we have used the simplest model of DPOAE generation and modulation, by assuming that the DPOAEs were generated by a 1st-order Boltzmann nonlinearity so that the magnitude of the 2f1-f2 DPOAE resembled the 3rd derivative of the Boltzmann function. We have also assumed that the modulation of the DPOAEs by the low-frequency tones was simply due to a sinusoidal change in the operating point on the Boltzmann nonlinearity. We have found the cyclic DPOAE modulation to be different in subjects with Ménière's syndrome (n = 16) when compared to the patterns in normal subjects (n = 16) and in other control subjects with non-Ménière's SNHL and/or vestibular disorders (n = 13). The DPOAEs of normal and non-Ménière's ears were suppressed more during negative ear canal pressure than during positive ear canal pressure. By contrast, DPOAE modulation in Ménière's ears with abnormal ECochG was greatest during positive ear canal pressures. This test may provide a tool for diagnosing Ménière's in the early stages, and might be used to investigate the pathological mechanism underlying the hearing symptoms of this syndrome.

Ocular vestibular evoked myogenic potentials in response to air-conducted sound in Ménière's disease.

BACKGROUND: Currently, Ménière's disease is predominantly diagnosed through clinical criteria. Additional standard vestibular testing, such as nystagmography, can show variable responses. In the last decade, the cervical vestibular evoked myogenic potential (VEMP) has shown to be of additive value in diagnosing Ménière's disease. In this study, the results of the ocular VEMP (oVEMP) in response to air-conducted sound will be discussed. OBJECTIVES: To evaluate possible changes of the oVEMP in a large group (n = 37) of patients with Ménière's disease. MATERIAL AND METHODS: In 55 subjects without Ménière's disease and 37 patients with Ménière's disease, oVEMPs in response to air-conducted sound stimulation (tone-burst, 500 Hz; maximum stimulus level, 120 dB sound pressure level) were studied. Recording was performed in upgaze with surface electrodes underneath both eyes. The burden of the test was scored by all subjects on a visual analogue scale. RESULTS: In patients with Ménière's disease the response rates are lower, the oVEMP amplitudes are smaller, and thresholds are higher than in subjects without Ménière's disease. This effect is observed in both ears of patients with Ménière's disease. The affected ear is more altered than the clinically unaffected ear. CONCLUSION: The air-conducted oVEMP can be a relevant addition to the current diagnostic workup of patients with possible Ménière's disease. A lower response rate, smaller amplitude, and higher threshold of the oVEMP indicate the pathologic disease in this population.