Potential Application of Ocular and Cervical Vestibular-Evoked Myogenic Potentials in Meniere s Disease: A Review

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1 The Laryngoscope VC 2012 The American Laryngological, Rhinological and Otological Society, Inc. Contemporary Review Potential Application of Ocular and Cervical Vestibular-Evoked Myogenic Potentials in Meniere s Disease: A Review Yi-Ho Young, MD By stimulating the ear with air-conducted sound or bone-conducted vibration stimuli, vestibular-evoked myogenic potential (VEMP) can be recorded on the contracted neck muscles, termed cervical VEMP (cvemp), and on the extraocular muscles, termed ocular VEMP (ovemp). These two electrophysiological tests expand the test battery for clinicians to explore the dynamic otolithic function, adding a potential usefulness to the sacculocollic reflex and vestibulo-ocular reflex, respectively. The inner ear test battery, including audiometry, and cvemp, ovemp and caloric tests, is designed for complete evaluation of the inner ear function, namely, the cochlea, saccule, utricle, and semicircular canals, respectively. Using this test battery to study the localization and prevalence of hydrops formation reveals that the declining function in the cochlea, saccule, utricle, and semicircular canals mimics the declining sequence of hydrops formation in temporal bone studies. This study reviewed the physiological results in Meniere s patients via the inner ear test battery, especially the potential application of the ovemp and cvemp tests, to correlate with the histopathological findings of Meniere s disease. Key Words: Cervical vestibular-evoked myogenic potential, ocular vestibular-evoked myogenic potential, Meniere s disease, endolymphatic hydrops, vestibular-evoked myogenic potential. Laryngoscope, 123: , 2013 From the Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan. Editor s Note: This Manuscript was accepted for publication July 11, The author has no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Yi-Ho Young, MD, Department of Otolaryngology, National Taiwan University Hospital, 1 Chang-te St., Taipei, Taiwan. youngyh@ntu.edu.tw DOI: /lary INTRODUCTION By stimulating the ear with air-conducted sound (ACS) or bone-conducted vibration (BCV) stimuli, vestibular-evoked myogenic potential (VEMP) can be recorded on the contracted neck muscles, so-called cervical VEMP (cvemp), and on the extraocular muscles, termed ocular VEMP (ovemp). 1 4 These two newly developed electrophysiological tests expand the test battery for clinicians to explore the dynamic otolithic function in the inner ear disorders, 5,6 adding a potential usefulness to the sacculocollic reflex and vestibulo-ocular reflex (VOR), respectively. 7 9 The ideal stimulation mode for cvemp testing is using ACS stimuli, whereas the optimal mode for ovemp testing is via BCV tapping. 6,10,11 Based on the hypothesis of efferent specificity proposed by Curthoys, 12 cvemps arise from the saccular macula, whereas ovemps primarily originate from the utricular macula. Animal models for cvemp and ovemp have been established in guinea pigs, which set the stage for evaluating the mechanism of utricular and saccular disorders in humans. 17 The recently developed inner ear test battery, which includes audiometry and cvemp, ovemp, and caloric tests, is designed for complete evaluation of the inner ear function, namely, the cochlea, saccule, utricle, and semicircular canals. 18 This test battery has been progressively utilized for clinical assessment in patients with Meniere s disease Using this test battery to study the localization and prevalence of hydrops formation reveals that the declining function in the cochlea, saccule, utricle, and semicircular canals 23 mimics the declining sequence of hydrops formation in temporal bone studies. 24 In addition, for patients with Meniere s disease who have intractable vertigo, the inner ear test battery provides detailed information about residual vestibular function, which is valuable when considering ablative treatments. 25 This study reviewed the physiological results in Meniere s patients from the inner ear test battery, especially the potential application of the ovemp and cvemp tests, to correlate with the histopathological findings of Meniere s disease. HYDROPS IN THE INNER EAR Cochlear Hydrops Acute low-tone hearing loss. Acute low-tone hearing loss (ALHL) is termed as idiopathic low-tone

2 Fig. 1. A 28-year-old female with Meniere s disease (left). The cervical vestibular-evoked myogenic potential (cvemp) test shows normal responses on the right ear (p13-n23 amplitude: 71 lv), and augmented responses on the left ear (p13-n23 amplitude: 157 lv), with the asymmetry ratio of 38%. sensorineural hearing loss of acute onset, with relatively preserved high-tone hearing. 26 By way of electrocochleography, the average summating potential to action potential ratio was high in patients with significant endolymphatic hydrops in the cochlea, 27 indicating that the pathophysiology of ALHL is attributed to the endolymphatic hydrops confined to the cochlea, especially at the apical turn, consistent with the histopathological evidence as a bulging of Reissner s membrane into the scala vestibuli of the cochlea apex. 28 In cases of ALHL, hearing loss usually improved soon after the onset of symptoms (<3 days), and tended to return to almost normal levels, possibly due to simply spontaneous recovery. Wu and Young 29 reported that 11 (92%) of 12 patients with ALHL revealed normal cvemps throughout the episode, indicating that the saccule is spared in most cases of ALHL. In contrast, augmented cvemps are sometimes demonstrated at the initial stage of Meniere s disease (Fig. 1), indicating dilatation of the saccular hydrops extending to be pressed against the footplate, because this action enhances the sensitivity of the saccular macula to loud sound. 30 Most patients with ALHL reveal normal cvemps throughout the episode, indicating that the saccule is spared. In contrast, 50% of Meniere s patients with low-tone hearing loss demonstrate abnormal cvemps, showing a significant difference. Therefore, a cvemp test can be used to differentiate ALHL from Meniere s disease with low-tone hearing loss. 29 Meniere s disease versus sudden deafness. Differentiation between sudden deafness and Meniere s disease is sometimes challenging, because both diseases have significant overlap in the symptoms. For example, the initial stage of Meniere s disease can be monosymptomatic at onset, with the occurrence of 22% for hearing loss only, 31 and one-third of them will develop vertiginous attack within 1 year. Thereby, when a Meniere s patient has acute sensorineural hearing loss initially, it may mimic sudden deafness. In addition to stapedial reflex test for checking the recruitment phenomenon, a cvemp test is proposed for differentiation between these two disease entities. 32 The cvemp test revealed abnormal percentages of 71% and 21% in patients with Meniere s disease and sudden deafness, respectively, exhibiting a significant difference because the transduction pathway of the cvemp is unrelated to the hearing level (i.e., cochlear nerve). 33 Nevertheless, cvemp test may help to predict the hearing outcome in cases of recurrent sudden deafness, including ipsilateral and contralateral types. Patients with recurrent sudden deafness demonstrating normal cvemps in the lesion ear of the second episode may indicate a good hearing outcome, because normal cvemps depict the lesion confined to the cochlea, 34 whereas absent or delayed cvemps imply a brainstem involvement. 35 Thus, the cvemp test can help to delineate the affected region and predict the hearing outcome in cases of recurrent sudden deafness. Meniere stage. According to the diagnostic criteria by American Academy of Otolaryngology, Head and Neck Surgery in 1995, 36 staging of Meniere s disease was based on the arithmetic mean of the pure-tone thresholds at 0.5, 1, 2, and 3 khz using the worst audiogram during the interval 6 months before treatment. Accordingly, stage I means four-tone average <26 db; stage II, 26 to 40 db; stage III, 41 to 70 db; and stage IV, >70 db. Clinically, fluctuating hearing loss plays a decisive role in the diagnosis of Meniere s disease, because endolymphatic hydrops occurs most often in the cochlear part. Low-frequency hearing loss is common in the early stage of Meniere s disease. Over time, high frequency hearing is also affected. Antoli-Candela 37 found that increased endolymphatic volume of the cochlear duct is directly related to hearing loss; a larger volume is common when hearing loss is >70 db HL. Next to the cochlea, the saccule is the second most frequent site for hydrops formation, and severe hydrops is observed most frequently in the saccule. 24 In the early stage of Meniere s disease, augmented cvemps (Fig. 1) may be attributed to a mechanical, biochemical, or some other reversible causes, 30 which can be reduced spontaneously or via administration of glycerol or furosemide However, in the late stage (stage IV) there are permanent morphological changes in the sense organs, including loss of saccular macula associated with collapse of the saccular wall onto the otolithic membrane, 41 which is consistent with reduced or absent cvemps (Fig. 2). Young et al. 20 reported that the interaural amplitude difference ratio (now termed asymmetry ratio) of cvemps increases significantly in terms of the stage of Meniere s disease. Therefore, the asymmetry ratio of cvemps, like four-tone average of hearing, shows promise in facilitating the stage of Meniere s disease. Saccular Hydrops Augmented cvemp. By stimulating the ear with loud sound or bone vibration and recording on tonically 485

3 Fig. 2. A 56-year-old female with Meniere s disease (right). The cervical vestibular-evoked myogenic potential (cvemp) test shows reduced responses (p13-n23 amplitude: 55 lv) on the right ear, but normal responses (p13-n23 amplitude: 125 lv) on the left ear, with the asymmetry ratio of 39%. contracted neck muscles, the cvemp test expands the vestibular test battery for clinicians to explore the saccular pathology. The cvemp is generated via a disynaptic pathway, beginning in the saccule and proceeding along vestibular afferent fibers to the vestibular nuclei, then via rapidly conducting projections that synapse with sternomastoid nuclei. 7,8 Because the cvemp amplitude p13-n23 varies substantially between subjects and in one subject between trials, asymmetry ratio (%) was used for comparison between both sides, which is defined as the difference of the p13-n23 amplitude on each ear divided by the sum of p13-n23 amplitude of both ears, that is: (larger amplitude smaller amplitude/larger amplitude þ smaller amplitude) 100. At our laboratory, the norm of asymmetry ratio of cvemps is % (mean 6 standard deviation [SD]), thus augmented cvemp is defined if the asymmetry ratio is >33%. 42 In human temporal bones affected by Meniere s disease, the saccular membrane bulged into the vestibule laterally, attached to the footplate of the stapes, and occupied the vestibular perilymphatic space. 24 Endolymphatic hydrops could have enhanced acoustic stimulation to the saccular macula by contacting the footplate with the distended saccule. With more extent of footplate attachment, endolymph is displaced more easily in hydropic ears, resulting in moderate or severe dilatation of hydrops, 31 and the sensitivity of the saccular macula to loud sound is thus enhanced. As cvemp amplitude has been demonstrated to relate to the intensity of acoustic stimulation, 43,44 cvemp was thereby augmented. Rauch et al. 45 reported that altered cvemp frequency tuning was noted in hydropic ears, which was due to hydropic structural distortion of the saccule. For example, hydropic ears showed less tuning at 500 Hz and shifted to the best frequency to 1,000 Hz. Thus, altered tuning provides another diagnostic parameter for Meniere s disease. 486 Delayed hydrops. Delayed endolymphatic hydrops (DEH) can be characterized as having ipsilateral and contralateral types. Ipsilateral DEH refers to one ear suffering from profound hearing loss. Following several years or decades, episodic vertigo occurs, accompanied by nausea/vomiting. 46,47 The contralateral DEH exhibits the same features of ipsilateral DEH and fluctuating hearing loss in the opposite better ear. 48 The mechanism of DEH is a sufficiently major labyrinthine insult to cause total deafness but preserve vestibular function, and to produce delayed atrophy or fibrous obliteration of the endolymph resorption system. Histopathological study of DEH demonstrated that the saccule was greatly dilated, with the saccular macula either severely degenerated, atrophied, or apparently normal. These findings correlate with cvemp results in cases of DEH, including absent cvemps 30%, reduced cvemps 25%, and normal cvemps 45%. 49 Thus, the presence of the saccular hydrops could produce either augmented or reduced cvemps depending on how atrophic the saccular macula is. 30,50 The presence of a normal cvemp implies that the sacculocollic reflex has retained normal conduction velocity; a normal saccule with intact saccular macula thus accounts for the presence of a normal cvemp. The dilated saccule with atrophied saccular macula is characterized by atrophy of the sensory epithelium, partial cellular encapsulation of the otolithic membrane, and a granular basophilic plaque overlying the supporting network of the macular epithelium. 48 Endolymph is displaced more easily in hydropic ears with extended footplate attachment, and this action enhances the sensitivity of the saccular macula to loud sound, resulting in augmented cvemps. However, those DEH ears without cvemps also provoked episodic vertigo, indicating that factors other than saccule prevail. As episodic vertigo disappeared in 90% of DEH patients within 10 years, 51 vertiginous attacks may subside spontaneously. For those with intractable vertigo, surgical labyrinthectomy or intratympanic gentamicin injections may be an alternative treatment for abolition of the vestibular function. 52 Thus, when a surgeon can identify the DEH stage, surgical intervention may be reserved in late-stage DEH patients. For patients with profound deafness and recalcitrant vertigo, surgical labyrinthectomy or gentamicin injection should be mentioned as a treatment option, and this may be reasonable early in the disease process because many DEH patients ultimately lose significant vestibular function. 53 Meniere attack. Acute vertiginous attack in Meniere s disease, the so-called Meniere attack, always brings the patient to the emergency room, where spontaneous nystagmus accompanied by nausea and vomiting is observed. Two mechanisms are proposed for the Meniere attack. One is membrane rupture theory, which mainly occurs on Reissner s membrane. 54 The other is the membrane distension theory, indicating that the utricular or saccular membrane herniates into the semicircular canal. 55 Although the occurrence of membrane rupture cannot be denied, especially when those present

4 grave accidents for hours, rupture of the endocochlear membrane, chiefly Reissner s membrane, fails to explain why high potassium concentration of endolymph bypasses the saccule into the semicircular canal to induce vertigo. Therefore, the saccular hydrops may precipitate the violent vertiginous attack in those with Meniere s disease. 56 When the saccular hydrops herniates into the horizontal semicircular canal (HSCC), high endolymphatic pressure presses on the cupula, leading to ampullopetal flow of the endolymph in the HSCC. Once the saccular hydrops releases after drainage or rupture, return of the cupula to a neutral position may cause ampullofugal flow in the HSCC. Furthermore, when the hydrops ruptures, the potassium-rich endolymph seeps onto the vestibular end organs and nerve endings. It is until the potassium is washed away and biochemistry reestablished, then spontaneous nystagmus vanishes. 54 Most (67%) patients with Meniere attacks reveal abnormal cvemps, indicating that the saccule participates in the event of Meniere attack, manifested as either distension or rupture of the saccular hydrops. 56 The abnormal cvemps may resolve and return to normal cvemps after a Meniere attack, indicating that the hair cells of the saccular macula remain intact throughout the attack. As the Meniere s disease progresses, saccular dysfunction can be noted as evidenced in reduced or absent cvemps on the affected ears in 54% of the Meniere s patients. 19,57 In addition to mechanical factors, Merchant et al. 58 reported that cellular or biochemical perturbations precede the onset of hydrops in Meniere s disease. These cellular perturbations cause dysfunction of the hydroionic homeostasis, resulting in hydrops and audiovestibular deficits. 59 Thus, either mechanical or electrochemical factors could explain the reduced or absent cvemps. Utricular Hydrops Subjective visual horizontal/subjective visual vertical versus ovemp tests. The ocular tilt reaction represents a fundamental pattern of coordinated eyehead roll motion based on the utricular and vertical canal inputs, which can be examined by subjective visual horizontal (SVH) or subjective visual vertical (SVV) test to reflect the static utricular function However, subjects may find visual cues to adjust their estimation of SVH/SVV during the test. Alternatively, the linear acceleration induced by BCV stimuli at Fz can be evaluated by ovemp test. As saccular neurons have a strong projection to neck muscles and a weak projection to the oculomotor system, neural connections in the sacculo-ocular system are relatively weak compared with neural connections in the utriculo-ocular and sacculocollic reflexes 63 ; thus, the ovemp test may reflect utricular macula activity. Unlike cvemp recorded on the neck muscle, ovemps can be recorded from the extraocular muscles in response to ACS or BCV stimuli 25,42,64 and is along the ascending vestibular pathway via a crossed VOR. 9,65 The elicitation of ovemp via BCV mode has recently been conducted in Meniere s patients. Significant correlation existed between SVH and ovemp test results, but not between SVH and cvemp test results, further supporting that SVH and ovemp tests may, at least in part, share the same utricular reflex pathway. 66 Caloric versus ovemp tests. The caloric test evaluates the rotational VOR system via the canal-ocular reflex. In contrast, the ovemp test assesses the translational VOR system via the otolithic-ocular reflex, which activates the otolithic maculae, then through the utricular branch of the superior vestibular nerve and a small branch from the hook portion of the saccule, and ascending via the vestibular nuclei to the opposite extraocular muscles. 67 The ovemp test results correlate significantly with caloric test results for acoustic neuroma patients, but not for Meniere s patients, indicating that ovemp test may replace the caloric test when evaluating from what vestibular nerve did the tumor arise. Conversely, caloric, ovemp, and cvemp tests should be performed to map the lesion sites in the inner ear of Meniere s disease. 68 Augmented ovemp. At our laboratory, the norm of asymmetry ratio of ovemp is % (mean 6 SD). Thus, responses with asymmetry ratio >40% are interpreted as augmented or reduced ovemp depending on whether the ni-pi amplitude of the lesion ear is larger or smaller than that of the opposite ear, respectively. Konishi 69 observed that the utriculo-endolymphatic (UE) valve opens for several days after hydrops formation begins and then closes due to the compression caused by increasing hydrops. The UE valve exists at the junction between the utricle and utricular duct. 70 Because the endolymph can easily flow in the direction from the utricular duct to the utricle but not in the reverse direction, the role of the UE valve is to maintain pressure in the utricle and semicircular canals. An acute pressure reduction in the saccule can collapse the pars superior (saccule and cochlear duct), but not the utricle. Therefore, endolymph pressure in the utricle can be maintained independently of the pressure in the pars superior. 71 Once the saccular membrane ruptures, collapsed or distorted saccule leads to absent or reduced cvemps. In this condition, the UE valve closes to maintain normal pressure of the utricle and semicircular canals. Thus, augmentation of ovemps (Fig. 3) may result from compensatory enlargement of the utricular hydrops as endolymph pressure from the utricle increases, indicating a transient and reversible status closer to the last Meniere attack. 71 After the inner ear regains its homeostasis, reopening of the UE valve may cause relief of the utricular hydrops. Consequently, augmented ovemps resolve and return to normal responses. Recently, Manzari et al. 22 also reported that dynamic utricular function in the hydropic ear is enhanced during a Meniere attack as evidenced by augmented ovemps, whereas dynamic saccular function in the hydropic ear is decreased as shown by reduced cvemps, which is a condition termed as dissociated VEMPs. 487

5 Meanwhile, the vestibular sense organs may also undergo severe atrophic changes. After repeated ruptures of the labyrinthine membrane, partial or total collapse of the membranous labyrinth ensued, which is a condition called vestibular atelectasis. 80 These histopathological findings can explain why spontaneous relief of vertigo occurs in the late stage of Meniere s disease. Nevertheless, hydrops presents less in the semicircular canals as evidenced in the pathological results. 81 Fig. 3. The same patient as in Figure 2 with Meniere s disease on the right ear. The ocular vestibular-evoked myogenic potential (ovemp) test demonstrates augmented responses (ni-pi amplitude: 22.1 lv) on the right ear, and normal responses (ni-pi amplitude: 7.1 lv) on the left ear, with the asymmetry ratio of 51%. ovemp by lateral tapping. By way of stimulation via ACS or BCV mode, ovemps have been successfully generated. 72 Notably, both stimulation modes act in two different ways. BCV stimulation applied to the head causes waves to travel around and through the head, and these waves result in linear accelerations at mastoids. 10 In contrast, ACS stimulation cannot induce acceleration, but acts by moving stapes and then causing endolymph flow. 73 Application of BCV stimuli to the forehead (Fz) stimulates the bilateral otolithic organs simultaneously. In contrast, tapping at the lateral mastoid (2 cm behind the opening of the external ear canal) may preferentially activate utricular afferents. 74,75 Further, tapping at the lateral mastoid site elicits relatively higher stimulus magnitude leading to earlier ovemp latencies and larger ovemp amplitudes when compared with tapping at Fz. 76 Tseng et al. 76 reported 14 Meniere s ears with absent ovemps when tapping at the Fz site. However, six of them turned out to be present ovemps when tapping at the lateral (affected) mastoid (Fig. 4), indicating that Meniere s ears require a stronger stimulus to elicit the ovemp than healthy ears. Restated, tapping at the Fz site is suggested to screen for the utricular function, whereas tapping at the lateral mastoid site is suitable for evaluating residual utricular function. Asymptomatic Hydrops in Unaffected Ears Using ACS stimuli in Meniere s patients, the low prevalence of normal ovemp (60%) and cvemp (85%) in unaffected (opposite) ears is a concern. 68 Like affected (hydropic) ears, ACS mode is unreliable in eliciting ovemp due to low-intensity sound stimuli. 82 In the case of cvemps, one may attribute the 15% prevalence of absent ACS-cVEMPs to an inadequate voluntary effect. Because the cvemp test was conducted with a background monitoring system, 83 the possibility of an inadequate muscular task can be excluded. Recently, Winters et al. 84 also reported that in patients with Meniere s disease the response rates are lower, the ovemp amplitudes are smaller, and thresholds are higher than in subjects without Meniere s disease. This effect is observed in both ears of patients with Meniere s disease. The affected ear is more altered than the clinically unaffected ear. Likewise, histopathological study also demonstrated that the contralateral inner ear in patients with unilateral Meniere s disease has significantly more damage compared with inner ears of normal controls. 85 Thus, asymptomatic hydrops in the unaffected ear is considered, 21 as evidenced by a pathological study that observed saccular hydrops in the asymptomatic ear of temporal bones from donors with unilateral Meniere s disease. 86 Canal Hydrops In addition to abnormal hearing, and ovemp and cvemp test results, reduction in caloric response is also associated with Meniere s disease. Stahle and Bergman 77 studied caloric reaction in 300 patients with Meniere s disease, and reduced caloric response was found in no more than 65%. Friberg et al. 78 reported that canal paresis was noted in 50% of Meniere s patients after the first decade. Rizvi 79 found that in the late stage of Meniere s disease, there might be severe dilatation or collapse of the ampullary walls, which would interfere with the cupular movement, resulting in a poor caloric response. 488 Fig. 4. A 44-year-old female with left Meniere s disease. The ocular vestibular-evoked myogenic potential (ovemp) test shows absent responses on the left side when tapping at Fz, which turns out to be responses via tapping at the lateral mastoid (lat). Right: control.

6 The average time for conversion from unilateral to bilateral Meniere s disease was 7.6 years. 87 Bilateral involvements increase with increasing duration of the Meniere s disease (up to 35% within 10 years and up to 47% within 20 years). 88 A temporal bone study revealed that 20 of 67 endolymphatic hydrops cases had bilateral involvements, suggesting a rate of bilaterality in Meniere s disease of about 30%. 89 Variants of Meniere s Disease Lermoyez s syndrome. Lermoyez s syndrome is defined as increasing illness, progressive deafness, then sudden vertigo and good hearing just as a thunderstorm clears a dark cloudy sky. 90 Obstruction of the ductus reunions may induce cochlear hydrops, resulting in symptoms such as fullness sensation, tinnitus, and hearing loss. 91 Once the pressure of the endolymph reaches a certain level, it forces the opening of the ductus reunions, allowing a large amount of endolymph to flow through UE valve into the utricle and semicircular canals, resulting in a vertiginous attack. 92 Thereafter, by releasing the endolymphatic pressure of the cochlear part, the cochlear symptoms subside. Manzari et al. 93 reported that reduced ovemps and stable cvemps were observed in Lermoyez s syndrome, opposite to augmented ovemps and reduced cvemps during Meniere attacks, providing physiological evidence to support that Lermoyez s syndrome is a variant of Meniere s disease. Tumarkin falls. Tumarkin falls are abrupt attacks of falling without loss of consciousness. 94 Such patients could immediately arise and resume their previous activities. Typically, these drop attacks occur instantaneously, manifested as the sensation of being pushed from behind or the environment suddenly moving. It lasts 1 minute or less, without warning or whirling motion, and is not associated with autonomic symptoms such as nausea, vomiting, pallor, or sweating. 95 In those with long-term Meniere s disease, the incidence of Tumarkin falls varies from 5% to 10%. 96 Because neither vertigo nor nystagmus was noted during drop attacks, the otolithic organs rather than the semicircular canals are considered to trigger the Tumarkin falls. It is thought to be the result of a sudden mechanical deformation of the otolithic membrane, leading to activation of motoneurons of vestibulospinal pathway. 97 In a long-term Meniere s patient, loss of hair cells associated with collapsed otolithic wall on the otolithic organs can be shown, which is consistent with absent cvemps and/or ovemps. Timmer et al. 98 reported that 41% of Meniere s patients with Tumarkin falls had absent cvemps. Further, Merchant and Schuknecht 80 reported a temporal bone study in a 44-year-old Meniere s patient having a tendency of tilting and falling. The histopathological study demonstrated severe cochleosaccular hydrops with the collapse of the utricular and ampullary walls. They attributed the persistent unsteadiness to the collapsed walls of the utricle and ampullae. Thus, with residual canal function (canal paresis) and absent cvemps, subsequent residual utricular function may trigger the Tumarkin falls in Meniere s patients. 99,100 CONCLUSION Those factors, such as the complexity of Meniere s disease, the uncertainty regarding pathophysiological mechanisms, and the variation in the initial presentation and time course of the disease across individuals, are likely to contribute to the variability seen in the audio-vestibular test results, which is why an inner ear test battery approach is so important. The inner ear test battery, including audiometry, and cvemp, ovemp and caloric tests, is designed for complete evaluation of the inner ear function, including the cochlea, saccule, utricle, and semicircular canals. It is believable that thorough investigation in Meniere s patients via the inner ear test battery may stimulate the elucidation of the mechanism of Meniere s disease. BIBLIOGRAPHY 1. Colebatch JG, Halmagyi GM, Skuse NF. 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