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Assessment of the otolith-ocular reflex using ocular vestibular evoked myogenic potentials in patients with episodic lateral tilt sensation
Neuroscience Letters 515 (2012) 103–106
Contents lists available at SciVerse ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Assessment of the otolith-ocular reflex using ocular vestibular evoked myogenic potentials in patients with episodic lateral tilt sensation Toshihisa Murofushi ∗ , Haruka Nakahara, Eriko Yoshimura Department of Otolaryngology, Teikyo University School of Medicine Mizonokuchi Hospital, 3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki 213-8507, Japan
a r t i c l e
i n f o
Article history: Received 15 November 2011 Received in revised form 20 February 2012 Accepted 26 February 2012 Keywords: Otolith Utricule Saccule VEMP oVEMP
a b s t r a c t The otolith-ocular reflex in patients with episodic lateral tilt sensation without any other vestibular symptoms was assessed using ocular vestibular evoked myogenic potentials (oVEMP). Ten patients (6 men and 4 women, mean age = 53.5) were enrolled. All patients had episodic lateral tilt sensation. Patients with a medical history of rotatory vertigo, loss of consciousness, head trauma, or symptoms or signs of central nervous dysfunction or proprioceptive dysfunction and those who had been definitely diagnosed with a disease that causes disequilibrium were excluded. All of the 10 patients had oVEMP tests and cervical VEMP (cVEMP) tests and underwent caloric tests. Eight of the 10 patients showed unilateral absence of oVEMP, one displayed a bilateral absence, and one displayed normal oVEMP. Concerning cVEMP, 4 patients showed a unilateral absence of cVEMP, one displayed unilaterally decreased responses and 5 displayed normal cVEMP. All patients showed normal bilateral caloric responses. The present study showed that patients with episodic lateral tilt sensation displayed abnormal otolith-ocular reflexes, as shown by their oVEMP, suggesting that these patients were suffering from utricular dysfunction. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Materials and methods
The vestibular labyrinth is composed of two otolith organs and 3 semicircular canals. The otolith organs, the utricle and saccule, act as sensors of linear acceleration. From the viewpoint of polarity, the utricular macula seems to be sensitive to lateral tilting [8]. Therefore, dysfunction of the utricular macula could lead to lateral tilt sensation. Thus, patients with episodic lateral tilt sensation without any other vestibular symptoms could be suffering from otolith organ dysfunction, especially utricular dysfunction, not their semicircular canal dysfunction. Vestibular evoked myogenic potentials around the eye (ocular VEMP, oVEMP) [3,13] and VEMP on the sternocleidomastoid muscle (cVEMP) [5,13] are utilized as clinical measures of otolith-ocular reflexes and otolith-collic reflexes, respectively. In order to study the association between episodic lateral tilt sensation and otolith organ dysfunction, especially utricular dysfunction, we recorded oVEMP and cVEMP in patients with episodic lateral tilt sensation without any other vestibular symptoms.
2.1. Patients Among patients presented with balance problems at our clinics, those who fulfilled the criteria described below were enrolled in this study. 2.1.1. Inclusion criterion Subjects had to have experienced episodic lateral tilt sensation including sensations of being pushed or pulled laterally. 2.1.2. Exclusion criteria Subjects with any of the following were excluded: 1. A medical history of rotatory vertigo. 2. A medical history of loss of consciousness or severe head trauma. 3. Symptoms or signs of central nervous system dysfunctions or proprioceptive dysfunctions. 4. A definitive diagnosis of a disease known to cause disequilibrium (e.g. Meniere’s disease, vestibular migraine, etc.). 2.2. Methods
∗ Corresponding author. Tel.: +81 44 844 3333; fax: +81 44 813 2257. E-mail address: [email protected] (T. Murofushi). 0304-3940/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2012.02.084
Patients who fulfilled the abovementioned criteria underwent tests including assessments of their oVEMP and cVEMP, and
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T. Murofushi et al. / Neuroscience Letters 515 (2012) 103–106
Table 1 Summary of enrolled subjects. No.
Age
Sex
Duration of each episode
oVEMP
cVEMP
Caloric tests
#1 #2 #3 #4 #5 #6 #7 #8 #9 #10
51 57 58 47 66 39 61 35 47 74
F M F M F M M F M M
1h A few minutes A few minutes 1h A few minutes A few minutes A few minutes 10 min 1 min A few minutes
NL NL NL NE NL NL NR Normal NL NR
NL Normal Normal NL NL NL Normal Normal LD Normal
Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
NL(R): No response to left (right) ear stimulation. NE: No response to stimulation of either ear. LD: Decreased responses to left ear stimulation.
caloric tests. The methods used to record oVEMP and cVEMP were described elsewhere [13]. Here, we describe the methods in brief. The Neuropack system (Nihon Kohden Co. Ltd., Japan) was used to record oVEMP and cVEMP. 2.2.1. oVEMP The recording electrodes were placed just beneath the lower eyelids (active) and 2 cm below the active electrodes (indifferent) with a ground electrode placed on the nasion. As acoustic stimuli, air-conducted 500 Hz short tone bursts (125 dBSPL, rise/fall time = 1 ms, plateau time = 2 ms) were presented through headphones (Type DR-531, Elega Acous Co. Ltd., Japan). The stimulation rate was 5 Hz. The subjects were asked to maintain an upward-gaze during recording. The signals were amplified, bandpass-filtered (20–2000 Hz), and 100 responses were averaged. The time window for recording was −20 ms to 80 ms. To confirm the reproducibility of the results, 2 runs were performed for each ear. The responses produced under the eye contralateral to the stimulated ear were assessed. We analyzed the first biphasic responses (nI–pI) [13]. In order to eliminate the effect of variations in muscle activity, the mean background amplitude was calculated from the mean rectified background activity during the 20 ms pre-stimulus period. The corrected amplitude (CA) of the oVEMP was defined using the following ratio in each run (amplitude of nI–pI)/(mean background amplitude) in each run. The corrected oVEMP amplitude (dimensionless) was employed for interaural comparisons. For these comparisons, the percent oVEMP asymmetry was calculated as follows. Percent oVEMP asymmetry = 100 |CAor − CAol|/(CAor + CAol). CAor(l) = corrected amplitude of nI–pI on the right (left) side. |CAor − CAol| represented the absolute value of CAor − CAol. According to a previous study recorded under the same conditions [13], the upper limit of the normal range of the percent oVEMP asymmetry was set as 44.3. 2.2.2. cVEMP To record cVEMP, electrodes were placed on the upper half of each sternocleidomastoid muscle (SCM), with a reference electrode on the lateral end of the upper sternum and a ground electrode on the nasion. During the recording, subjects in the supine position were instructed to raise their heads from the pillow to contract the SCM. The other aspects of the recording method were the same as those used to record oVEMP. We analyzed the first biphasic responses (p13–n23). The corrected cVEMP amplitude (dimensionless) was employed for interaural comparisons.
Percent cVEMP asymmetry = 100 |CAcr − CAcl|/(CAcr + CAcl). CAcr(l) = corrected amplitude of p13–n23 on the right (left). |CAcr − CAcl| represented the absolute value of CAcr − CAcl. According to a previous study recorded under the same conditions [13], the upper limit of the normal range of percent cVEMP asymmetry was set as 41.6.
2.2.3. Caloric tests Caloric tests were performed in a dark room using electronystagmography (ENG) by irrigating the external ear canal with cold water. Canal paresis (CP) in the caloric test was calculated using the maximum slow phase eye velocity of caloric nystagmus. Informed consents were obtained from all subjects. Ethical approval was received from the Teikyo University Ethics Committee.
3. Results 3.1. Patients’ profiles Ten patients (6 males and 4 females) fulfilled the criteria (Table 1). Their ages ranged from 35 to 74 (average 53.5). The duration of each episode ranged from 1-min to 1-h. The majority of patients stated that their attacks lasted for a few minutes.
3.2. oVEMP Among the 10 patients, 8 patients did not show an oVEMP response on one side (right:left = 2:6) (Fig. 1), one did not display oVEMP responses on either side, and one showed bilateral normal responses.
3.3. cVEMP Among the 10 patients, 4 patients did not display a cVEMP response on one side (right:left = 0:4). Note that the sides of ears which showed absent responses were identical to oVEMP. One showed unilaterally decreased responses, and 5 showed normal bilateral responses.
3.4. Caloric tests All of the patients showed normal bilateral caloric responses.
T. Murofushi et al. / Neuroscience Letters 515 (2012) 103–106
105
Fig. 1. oVEMP and cVEMP of #2 (57-year-old man). This patient showed an absence of oVEMP responses to left ear stimulation while his bilateral cVEMP responses were normal.
4. Discussion The present study revealed that the majority of patients (9 out of 10) that experienced episodic lateral tilt sensation without any other vestibular symptoms showed abnormal oVEMP in response to air-conducted sound (ACS), while 5 showed abnormal cVEMP in response to ACS. None of the enrolled patients showed abnormal caloric responses. These results suggest that ACS-induced oVEMP can be used to sensitively detect dysfunction associated with episodic lateral tilt sensation. Although the origin of ACS-induced oVEMP is disputed, Murofushi et al. suggested that ACS-induced oVEMP predominantly reflects utricular function while AC-induced cVEMP predominantly reflects saccular functions [13]. Murofushi et al. [13] showed that ACS-induced oVEMP results and ACS-induced cVEMP results are independent of each other in patients with Meniere’s disease (MD) and that only 2 of the 6 patients with vestibular neuritis (VN) showed abnormal ACS-induced cVEMPs while all the 6 patients with VN had abnormal ACS-induced oVEMPs. These results suggested that ACS-induced oVEMP predominantly reflect utricular functions because VN often affects superior vestibular nerve with sparing inferior vestibular nerve function [9]. The studies of oVEMP and cVEMP in VN patients by Shin et al. [16] and Curthoys et al. [6] supported the hypothesis that oVEMP predominantly reflects utricular functions. On the other hand, Govender et al. [10] proposed that the dissociation of ACS-induced oVEMP findings and ACS-induced cVEMP findings in VN patients might be caused by disorders of saccular afferents in the superior vestibular nerve, which arise from the antero-superior part of the saccule. While this hypothesis could explain the dissociation in the VN patients, it is hard to explain the dissociation in MD patients [13], because the lesion site of MD is not in the vestibular nerve but in the inner ear. Colebatch [4] proposed that facilitation of saccular afferents by utricular afferents is required to produce ACS-induced oVEMP. This hypothesis does not explain the results that some MD patients showed abnormal ACS-induced cVEMP but normal ACS-induced oVEMP [13]. Lateral tilt sensation is likely to be caused by utricular dysfunction because the polarity of vestibular afferents from the utricular macula is more trans-aural dominant than the polarity of those from the saccular macula [8,11]. In addition, a study of eccentric rotation indicated that trans-aural linear force caused lateral tilt sensation [7,14]. Therefore, our finding in this study that patients with episodic lateral tilt sensation without any other vestibular symptoms predominantly demonstrated abnormal results during oVEMP testing indicates that episodic lateral tilt sensation is caused by utricular dysfunction. We would like to propose “idiopathic utricular dysfunction” as a tentative diagnostic term representing conditions involving episodic lateral tilt sensation without any other vestibular symptoms. At least nine of the 10 patients in this study (except for No. 8) had idiopathic utricular dysfunction.
Among the 10 patients, 5 patients also had abnormal cVEMP results. These patients might have also saccular dysfunction. Saccular dysfunction could cause antero-posterior tilt sensation or up-down sensation. At the present stage, the reasons why the patients enrolled in this study did not have such sensations are not known. In the future study, patients presented with antero-posterior tilt sensation or up-down sensation should be investigated. What is the pathological or pathophysiological basis of “idiopathic utricular dysfunction? First of all, endolymphatic hydrops such as MD should be taken into consideration. MD could cause sudden falls without loss of consciousness, which is known as Tumarkin’s otolithic crisis (vestibular drop attack) [15,17]. Although our patients did not meet the criteria of definite MD [1], they might be diagnosed as having MD in the future. It is reported that hydrops in the saccule and cochlea could often precede hydrops in the utricle in MD patients [12]. Patients in this study might be MD with atypical clinical course. Brandt reported otolith type of perilymph fistula [2]. Perilymph fistula is another possible cause of “idiopathic utricular dysfunction”, although none of the patients in this study suffered from episodes that were suggestive of a perilymph fistula. Although Brandt also described that head trauma might cause otolithic vertigo [2], our patients did not experience severe head trauma, either.
5. Conclusion In conclusion, the present study showed that patients with episodic lateral tilt sensation displayed abnormal otolith-ocular reflexes shown by their oVEMP, suggesting that these patients were suffering from utricular dysfunction. We propose that these patients should be categorized as having “idiopathic utricular dysfunction”. In order to clarify the pathophysiology underlying “idiopathic utricular dysfunction”, further observation and extensive studies will be required.
References [1] AAO-HNS guidelines for the evaluation of therapy in Meniere’s disease, Otolaryngol. Head Neck Surg. 113 (1995) 181–185. [2] T. Brandt, Otolithic vertigo, Adv. Otorhinolaryngol. 58 (2001) 34–47. [3] Y. Chihara, M. Ushio, S. Iwasaki, T. Murofushi, Vestibular-evoked extraocular potentials by air-conducted sound: another clinical test of the vestibular function, Clin. Neurophysiol. 118 (2007) 2745–2751. [4] J.G. Colebatch, Sound conclusion? Clin. Neurophysiol. 121 (2010) 124–126. [5] J.G. Colebatch, G.M. Halmagyi, N.F. Skuse, Myogenic potentials generated by a click-evoked vestibulocollic reflex, J. Neurol. Neurosurg. Psychiatry 57 (1994) 190–197. [6] I.S. Curthoys, S. Iwasaki, Y. Chihara, M. Ushio, L.A. McGarvie, A.M. Burgess, The ocular vestibular-evoked myogenic potential to air-conducted sound; probable superior vestibular nerve origin, Clin. Neurophysiol. 122 (2011) 611–616.
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[7] M.J. Dai, I.S. Curthoy, G.M. Halmagyi, Linear acceleration perception in the roll plane before and after unilateral vestibular neurectomy, Exp. Brain Res. 77 (1989) 315–328. [8] C. Fernandez, J.M. Goldberg, Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. I. Response to static tilts and to long-duration centrifugal force, J. Neurophysiol. 39 (1976) 970–984. [9] M. Fetter, J. Dichgans, Vestibular neuritis spares the inferior division of the vestibular nerve, Brain 113 (1996) 755–763. [10] S. Govender, S.M. Rosengren, J.G. Colebatch, Vestibular neuritis has selective effects on air- and bone-conducted cervical and ocular vestibular evoked myogenic potentials, Clin. Neurophysiol. 122 (2011) 1246–1255. [11] M.A. Gresty, A.M. Bronstein, T. Brandt, M. Dieterich, Neurology of otolith function: peripheral and central disorders, Brain 115 (1992) 647–673. [12] M.Y. Lin, F.C.A. Timmer, B.S. Oriel, G. Zhou, J.J. Guinan, S.G. Kujawa, B.S. Herrmann, S.N. Merchant, S.D. Rauch, Vestibular evoked myogenic potentials
[13]
[14]
[15]
[16]
[17]
(VEMP) can detect asymptomatic saccular hydrops, Laryngoscope 116 (2006) 987–992. T. Murofushi, H. Nakahara, E. Yoshimura, Y. Tsuda, Association of air-conducted sound oVEMP findings with cVEMP and caloric test findings in patients with unilateral peripheral vestibular disorders, Acta Otolaryngol. 131 (2011) 945–950. L.M. Odkvist, M.A. Gripmark, B. Larsby, T. Ledin, The subjective horizontal in eccentric rotation influenced by peripheral vestibular lesion, Acta Otolaryngol. 116 (1996) 181–184. H. Ozeki, S. Iwasaki, T. Murofushi, Vestibular drop attack secondary to Meniere’s disease results from unstable otolithic function, Acta Otolaryngol. 128 (2008) 887–891. B.S. Shin, S.Y. Oh, J.S. Kim, T.W. Kim, M.W. Seo, H. Lee, Y.A. Park, Cervical and ocular vestibular-evoked myogenic potentials in acute vestibular neuritis, Clin. Neurophysiol. 123 (2012) 369–375. A. Tumarkin, The otolithic cathastrophe: a new syndrome, Br. Med. J. 1 (1936) 175–177.
Contents lists available at SciVerse ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Assessment of the otolith-ocular reflex using ocular vestibular evoked myogenic potentials in patients with episodic lateral tilt sensation Toshihisa Murofushi ∗ , Haruka Nakahara, Eriko Yoshimura Department of Otolaryngology, Teikyo University School of Medicine Mizonokuchi Hospital, 3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki 213-8507, Japan
a r t i c l e
i n f o
Article history: Received 15 November 2011 Received in revised form 20 February 2012 Accepted 26 February 2012 Keywords: Otolith Utricule Saccule VEMP oVEMP
a b s t r a c t The otolith-ocular reflex in patients with episodic lateral tilt sensation without any other vestibular symptoms was assessed using ocular vestibular evoked myogenic potentials (oVEMP). Ten patients (6 men and 4 women, mean age = 53.5) were enrolled. All patients had episodic lateral tilt sensation. Patients with a medical history of rotatory vertigo, loss of consciousness, head trauma, or symptoms or signs of central nervous dysfunction or proprioceptive dysfunction and those who had been definitely diagnosed with a disease that causes disequilibrium were excluded. All of the 10 patients had oVEMP tests and cervical VEMP (cVEMP) tests and underwent caloric tests. Eight of the 10 patients showed unilateral absence of oVEMP, one displayed a bilateral absence, and one displayed normal oVEMP. Concerning cVEMP, 4 patients showed a unilateral absence of cVEMP, one displayed unilaterally decreased responses and 5 displayed normal cVEMP. All patients showed normal bilateral caloric responses. The present study showed that patients with episodic lateral tilt sensation displayed abnormal otolith-ocular reflexes, as shown by their oVEMP, suggesting that these patients were suffering from utricular dysfunction. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Materials and methods
The vestibular labyrinth is composed of two otolith organs and 3 semicircular canals. The otolith organs, the utricle and saccule, act as sensors of linear acceleration. From the viewpoint of polarity, the utricular macula seems to be sensitive to lateral tilting [8]. Therefore, dysfunction of the utricular macula could lead to lateral tilt sensation. Thus, patients with episodic lateral tilt sensation without any other vestibular symptoms could be suffering from otolith organ dysfunction, especially utricular dysfunction, not their semicircular canal dysfunction. Vestibular evoked myogenic potentials around the eye (ocular VEMP, oVEMP) [3,13] and VEMP on the sternocleidomastoid muscle (cVEMP) [5,13] are utilized as clinical measures of otolith-ocular reflexes and otolith-collic reflexes, respectively. In order to study the association between episodic lateral tilt sensation and otolith organ dysfunction, especially utricular dysfunction, we recorded oVEMP and cVEMP in patients with episodic lateral tilt sensation without any other vestibular symptoms.
2.1. Patients Among patients presented with balance problems at our clinics, those who fulfilled the criteria described below were enrolled in this study. 2.1.1. Inclusion criterion Subjects had to have experienced episodic lateral tilt sensation including sensations of being pushed or pulled laterally. 2.1.2. Exclusion criteria Subjects with any of the following were excluded: 1. A medical history of rotatory vertigo. 2. A medical history of loss of consciousness or severe head trauma. 3. Symptoms or signs of central nervous system dysfunctions or proprioceptive dysfunctions. 4. A definitive diagnosis of a disease known to cause disequilibrium (e.g. Meniere’s disease, vestibular migraine, etc.). 2.2. Methods
∗ Corresponding author. Tel.: +81 44 844 3333; fax: +81 44 813 2257. E-mail address: [email protected] (T. Murofushi). 0304-3940/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2012.02.084
Patients who fulfilled the abovementioned criteria underwent tests including assessments of their oVEMP and cVEMP, and
104
T. Murofushi et al. / Neuroscience Letters 515 (2012) 103–106
Table 1 Summary of enrolled subjects. No.
Age
Sex
Duration of each episode
oVEMP
cVEMP
Caloric tests
#1 #2 #3 #4 #5 #6 #7 #8 #9 #10
51 57 58 47 66 39 61 35 47 74
F M F M F M M F M M
1h A few minutes A few minutes 1h A few minutes A few minutes A few minutes 10 min 1 min A few minutes
NL NL NL NE NL NL NR Normal NL NR
NL Normal Normal NL NL NL Normal Normal LD Normal
Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
NL(R): No response to left (right) ear stimulation. NE: No response to stimulation of either ear. LD: Decreased responses to left ear stimulation.
caloric tests. The methods used to record oVEMP and cVEMP were described elsewhere [13]. Here, we describe the methods in brief. The Neuropack system (Nihon Kohden Co. Ltd., Japan) was used to record oVEMP and cVEMP. 2.2.1. oVEMP The recording electrodes were placed just beneath the lower eyelids (active) and 2 cm below the active electrodes (indifferent) with a ground electrode placed on the nasion. As acoustic stimuli, air-conducted 500 Hz short tone bursts (125 dBSPL, rise/fall time = 1 ms, plateau time = 2 ms) were presented through headphones (Type DR-531, Elega Acous Co. Ltd., Japan). The stimulation rate was 5 Hz. The subjects were asked to maintain an upward-gaze during recording. The signals were amplified, bandpass-filtered (20–2000 Hz), and 100 responses were averaged. The time window for recording was −20 ms to 80 ms. To confirm the reproducibility of the results, 2 runs were performed for each ear. The responses produced under the eye contralateral to the stimulated ear were assessed. We analyzed the first biphasic responses (nI–pI) [13]. In order to eliminate the effect of variations in muscle activity, the mean background amplitude was calculated from the mean rectified background activity during the 20 ms pre-stimulus period. The corrected amplitude (CA) of the oVEMP was defined using the following ratio in each run (amplitude of nI–pI)/(mean background amplitude) in each run. The corrected oVEMP amplitude (dimensionless) was employed for interaural comparisons. For these comparisons, the percent oVEMP asymmetry was calculated as follows. Percent oVEMP asymmetry = 100 |CAor − CAol|/(CAor + CAol). CAor(l) = corrected amplitude of nI–pI on the right (left) side. |CAor − CAol| represented the absolute value of CAor − CAol. According to a previous study recorded under the same conditions [13], the upper limit of the normal range of the percent oVEMP asymmetry was set as 44.3. 2.2.2. cVEMP To record cVEMP, electrodes were placed on the upper half of each sternocleidomastoid muscle (SCM), with a reference electrode on the lateral end of the upper sternum and a ground electrode on the nasion. During the recording, subjects in the supine position were instructed to raise their heads from the pillow to contract the SCM. The other aspects of the recording method were the same as those used to record oVEMP. We analyzed the first biphasic responses (p13–n23). The corrected cVEMP amplitude (dimensionless) was employed for interaural comparisons.
Percent cVEMP asymmetry = 100 |CAcr − CAcl|/(CAcr + CAcl). CAcr(l) = corrected amplitude of p13–n23 on the right (left). |CAcr − CAcl| represented the absolute value of CAcr − CAcl. According to a previous study recorded under the same conditions [13], the upper limit of the normal range of percent cVEMP asymmetry was set as 41.6.
2.2.3. Caloric tests Caloric tests were performed in a dark room using electronystagmography (ENG) by irrigating the external ear canal with cold water. Canal paresis (CP) in the caloric test was calculated using the maximum slow phase eye velocity of caloric nystagmus. Informed consents were obtained from all subjects. Ethical approval was received from the Teikyo University Ethics Committee.
3. Results 3.1. Patients’ profiles Ten patients (6 males and 4 females) fulfilled the criteria (Table 1). Their ages ranged from 35 to 74 (average 53.5). The duration of each episode ranged from 1-min to 1-h. The majority of patients stated that their attacks lasted for a few minutes.
3.2. oVEMP Among the 10 patients, 8 patients did not show an oVEMP response on one side (right:left = 2:6) (Fig. 1), one did not display oVEMP responses on either side, and one showed bilateral normal responses.
3.3. cVEMP Among the 10 patients, 4 patients did not display a cVEMP response on one side (right:left = 0:4). Note that the sides of ears which showed absent responses were identical to oVEMP. One showed unilaterally decreased responses, and 5 showed normal bilateral responses.
3.4. Caloric tests All of the patients showed normal bilateral caloric responses.
T. Murofushi et al. / Neuroscience Letters 515 (2012) 103–106
105
Fig. 1. oVEMP and cVEMP of #2 (57-year-old man). This patient showed an absence of oVEMP responses to left ear stimulation while his bilateral cVEMP responses were normal.
4. Discussion The present study revealed that the majority of patients (9 out of 10) that experienced episodic lateral tilt sensation without any other vestibular symptoms showed abnormal oVEMP in response to air-conducted sound (ACS), while 5 showed abnormal cVEMP in response to ACS. None of the enrolled patients showed abnormal caloric responses. These results suggest that ACS-induced oVEMP can be used to sensitively detect dysfunction associated with episodic lateral tilt sensation. Although the origin of ACS-induced oVEMP is disputed, Murofushi et al. suggested that ACS-induced oVEMP predominantly reflects utricular function while AC-induced cVEMP predominantly reflects saccular functions [13]. Murofushi et al. [13] showed that ACS-induced oVEMP results and ACS-induced cVEMP results are independent of each other in patients with Meniere’s disease (MD) and that only 2 of the 6 patients with vestibular neuritis (VN) showed abnormal ACS-induced cVEMPs while all the 6 patients with VN had abnormal ACS-induced oVEMPs. These results suggested that ACS-induced oVEMP predominantly reflect utricular functions because VN often affects superior vestibular nerve with sparing inferior vestibular nerve function [9]. The studies of oVEMP and cVEMP in VN patients by Shin et al. [16] and Curthoys et al. [6] supported the hypothesis that oVEMP predominantly reflects utricular functions. On the other hand, Govender et al. [10] proposed that the dissociation of ACS-induced oVEMP findings and ACS-induced cVEMP findings in VN patients might be caused by disorders of saccular afferents in the superior vestibular nerve, which arise from the antero-superior part of the saccule. While this hypothesis could explain the dissociation in the VN patients, it is hard to explain the dissociation in MD patients [13], because the lesion site of MD is not in the vestibular nerve but in the inner ear. Colebatch [4] proposed that facilitation of saccular afferents by utricular afferents is required to produce ACS-induced oVEMP. This hypothesis does not explain the results that some MD patients showed abnormal ACS-induced cVEMP but normal ACS-induced oVEMP [13]. Lateral tilt sensation is likely to be caused by utricular dysfunction because the polarity of vestibular afferents from the utricular macula is more trans-aural dominant than the polarity of those from the saccular macula [8,11]. In addition, a study of eccentric rotation indicated that trans-aural linear force caused lateral tilt sensation [7,14]. Therefore, our finding in this study that patients with episodic lateral tilt sensation without any other vestibular symptoms predominantly demonstrated abnormal results during oVEMP testing indicates that episodic lateral tilt sensation is caused by utricular dysfunction. We would like to propose “idiopathic utricular dysfunction” as a tentative diagnostic term representing conditions involving episodic lateral tilt sensation without any other vestibular symptoms. At least nine of the 10 patients in this study (except for No. 8) had idiopathic utricular dysfunction.
Among the 10 patients, 5 patients also had abnormal cVEMP results. These patients might have also saccular dysfunction. Saccular dysfunction could cause antero-posterior tilt sensation or up-down sensation. At the present stage, the reasons why the patients enrolled in this study did not have such sensations are not known. In the future study, patients presented with antero-posterior tilt sensation or up-down sensation should be investigated. What is the pathological or pathophysiological basis of “idiopathic utricular dysfunction? First of all, endolymphatic hydrops such as MD should be taken into consideration. MD could cause sudden falls without loss of consciousness, which is known as Tumarkin’s otolithic crisis (vestibular drop attack) [15,17]. Although our patients did not meet the criteria of definite MD [1], they might be diagnosed as having MD in the future. It is reported that hydrops in the saccule and cochlea could often precede hydrops in the utricle in MD patients [12]. Patients in this study might be MD with atypical clinical course. Brandt reported otolith type of perilymph fistula [2]. Perilymph fistula is another possible cause of “idiopathic utricular dysfunction”, although none of the patients in this study suffered from episodes that were suggestive of a perilymph fistula. Although Brandt also described that head trauma might cause otolithic vertigo [2], our patients did not experience severe head trauma, either.
5. Conclusion In conclusion, the present study showed that patients with episodic lateral tilt sensation displayed abnormal otolith-ocular reflexes shown by their oVEMP, suggesting that these patients were suffering from utricular dysfunction. We propose that these patients should be categorized as having “idiopathic utricular dysfunction”. In order to clarify the pathophysiology underlying “idiopathic utricular dysfunction”, further observation and extensive studies will be required.
References [1] AAO-HNS guidelines for the evaluation of therapy in Meniere’s disease, Otolaryngol. Head Neck Surg. 113 (1995) 181–185. [2] T. Brandt, Otolithic vertigo, Adv. Otorhinolaryngol. 58 (2001) 34–47. [3] Y. Chihara, M. Ushio, S. Iwasaki, T. Murofushi, Vestibular-evoked extraocular potentials by air-conducted sound: another clinical test of the vestibular function, Clin. Neurophysiol. 118 (2007) 2745–2751. [4] J.G. Colebatch, Sound conclusion? Clin. Neurophysiol. 121 (2010) 124–126. [5] J.G. Colebatch, G.M. Halmagyi, N.F. Skuse, Myogenic potentials generated by a click-evoked vestibulocollic reflex, J. Neurol. Neurosurg. Psychiatry 57 (1994) 190–197. [6] I.S. Curthoys, S. Iwasaki, Y. Chihara, M. Ushio, L.A. McGarvie, A.M. Burgess, The ocular vestibular-evoked myogenic potential to air-conducted sound; probable superior vestibular nerve origin, Clin. Neurophysiol. 122 (2011) 611–616.
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