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Acta Oto-Laryngologica, 2011; 131: 945–950

ORIGINAL ARTICLE

Association of air-conducted sound oVEMP findings with cVEMP and


caloric test findings in patients with unilateral peripheral vestibular
disorders

TOSHIHISA MUROFUSHI1, HARUKA NAKAHARA1, ERIKO YOSHIMURA2 &


YUKIKO TSUDA2
1
Department of Otolaryngology, Teikyo University School of Medicine Mizonokuchi Hospital, Kawasaki and 2Yoshimura
ENT Clinic, Fujisawa, Japan

Abstract
Conclusion: This study showed that the ocular vestibular evoked myogenic potential (oVEMP) in response to
air-conducted sound (ACS) reflects functions of different parts of the vestibular labyrinth from cervical VEMP (cVEMP).
Objective: To determine whether the origin of the vestibular end organs of the oVEMP in response to ACS (500 Hz tone bursts)
is the same as that of cVEMP. Methods: Twenty patients definitively diagnosed with unilateral Meniere’s disease (MD),
6 patients with unilateral vestibular neuritis (VN), and 7 healthy subjects were enrolled. In these subjects, the oVEMP and
cVEMP to air-conducted 500 Hz tone bursts (125 dBSPL) were measured. The patients also underwent caloric tests. Results:
The MD patients did not show a significant association between their ACS oVEMP findings and ACS cVEMP findings but
there was an association of ACS oVEMP findings with caloric test findings. When the MD patients were classified into four
stages based on their hearing levels, the patients showed abnormal findings at earlier stages on ACS cVEMP than on other tests.
While all six VN patients showed abnormal findings on ACS oVEMP and caloric tests, only two patients showed abnormal
ACS cVEMPs. These findings support the hypothesis that the oVEMP in response to ACS predominantly reflects utricular
functions while ACS cVEMP reflects saccular functions.

Keywords: Meniere’s disease, vestibular neuritis, otolith, evoked responses, saccule, utricle, vestibular nerve, VEMP

Introduction Meniere’s disease (MD) is a representative disease


of the inner ear, while vestibular neuritis (VN) mainly
Vestibular evoked myogenic potentials in the cervical produces lesions in the vestibular nerve [9]. To clarify
muscles (cVEMP) have been used as a clinical test of the whether ACS oVEMP reflects the functions of dif-
vestibulo-collic reflex, predominantly sacculo-collic ferent components of the vestibular end organs from
reflex [1,2]. Recently, myogenic potentials around the ACS cVEMP, we studied patients with unilateral MD
eyes (oVEMP) have also been recorded using air- and unilateral VN. If the current hypothesis that ACS
conducted sound (ACS) as well as bone-conducted oVEMP reflects functions of the utricle and ACS
sound (BCS) [3,4]. Previous studies have suggested cVEMP reflects those of the saccule is correct,
that oVEMP and cVEMP reflect the functions of dif- ACS oVEMP findings and ACS cVEMP findings
ferent vestibular end organs. While studies concerning should be independent of each other. Furthermore,
the oVEMP produced in response to BCS have been ACS oVEMP findings should correlate with caloric
developed [5,6], there are few studies of oVEMP in test findings in VN patients, because both afferents
response to ACS [4,7,8]. The clinical significance of of the lateral semicircular canal and the utricle are
oVEMP in response to ACS remains unclear. involved in the superior vestibular nerve. Herein we

Correspondence: Prof. Toshihisa Murofushi, Department of Otolaryngology, Teikyo University School of Medicine, Mizonokuchi Hospital, 3-8-3 Mizonokuchi
Takatsu-ku, Kawasaki 213-8507, Japan. Tel: +81 44 844 3333. Fax: +81 44 813 2257. E-mail: toshi-tky@umin.ac.jp

(Received 15 January 2011; accepted 20 March 2011)


ISSN 0001-6489 print/ISSN 1651-2251 online  2011 Informa Healthcare
DOI: 10.3109/00016489.2011.580003
946 T. Murofushi et al.

report the associations among the findings of three n23


neuro-otological tests in patients with MD and VN.

Material and methods p13


200 µV

Subjects nl 10 ms

Twenty-six patients definitively diagnosed with uni-


lateral MD or unilateral VN were enrolled into this
pl
study. Twenty patients (2 men and 18 women) had stim.
unilateral MD and 6 patients (5 men and 1 woman) 2 µV
had unilateral VN. The patients’ ages ranged from 10 ms
31 to 94 years (mean 60.8) in MD and from 41 to
77 years (mean 61.3) in VN. Patients with conductive Figure 1. cVEMP and oVEMP of a healthy subject (51-year-old
man, left ear stimulation). The upper trace shows cVEMP on the
hearing loss were not included. The diagnoses of MD left sternocleidomastoid muscle, and the lower trace shows oVEMP
were based on the AAO-HNS guidelines (1995) [10]. below the right eye.
The diagnostic criteria for VN were the same as those
used in a previous study [11]; i.e. a single attack of
acute spontaneous vertigo lasting at least several the average rectified background activity during the
hours without accompanying auditory symptoms, pre-stimulus period of 20 ms as previously described
the absence of other cranial nerve or central nervous for cVEMP [12]. The corrected amplitude (CA) of
system symptoms or signs, and severe canal paresis the oVEMP was defined as a ratio of (amplitude of
(CP) on caloric testing (>50%). nI–pI)/(mean background amplitude) in each run.
We also recorded cVEMP and oVEMP of seven The corrected oVEMP amplitude (dimensionless)
healthy subjects (one man and six women) under the was employed for interaural comparisons. For these
same conditions as the patients. Control subjects’ comparisons, the percent oVEMP asymmetry was
ages ranged from 34 to 51 years (mean 46.5). calculated as follows.
Informed consent was obtained from each subject Percent oVEMP asymmetry = 100 |CAor–CAol|/
according to the Declaration of Helsinki. Ethical (CAor+CAol) (healthy subjects)
approval was received from the Teikyo University Percent oVEMP asymmetry = 100 (CAou–CAoa)/
Ethics Committee. (CAou+CAoa) (patients)
CAor(l) = corrected amplitude of nI–pI on the right
oVEMP (left)
CAou(a) = corrected amplitude of nI–pI on the
For recording of oVEMP as well as cVEMP, the unaffected (affected) side
Neuro-pack system (Nihon Kohden Co. Ltd, Japan) |CAor–CAol| represented the absolute value of
was used. The recording electrodes were placed just CAor–CAol.
beneath the lower eye lids (active) and 2 cm below the
active electrodes (indifferent) with a ground electrode cVEMP
on the nasion. As acoustic stimuli, air-conducted
500 Hz short tone bursts (125 dBSPL, rise/fall For recording cVEMPs, electrodes were placed on
time = 1 ms, plateau time = 2 ms) were presented the upper half of each sternocleidomastoid muscle
through headphones (Type DR-531, Elega Acous. Co. (SCM), with a reference electrode on the lateral end
Ltd, Japan). The stimulation rate was 5 Hz. Dur- of the upper sternum and a ground electrode on
ing recording, the subject was asked to maintain an the nasion. During the recording, subjects in the
upward gaze. The signals were amplified, bandpass- supine position were instructed to raise their heads
filtered (20–2000 Hz), and 100 responses were aver- from the pillow to contract the SCM. The other
aged. The time window for recording was –20 ms to aspects of the recording method were the same as
80 ms. To confirm the reproducibility of the results, those for oVEMP. We analyzed the first biphasic
two runs were performed on each ear. As described in a responses (p13–n23) (Figure 1). The mean back-
previous report [4], recordings obtained under the eye ground amplitude was also calculated from the
contralateral to the stimulated ear were assessed. We average rectified background activity during a pre-
analyzed the first biphasic responses (nI–pI) (Figure 1). stimulus period of 20 ms. The corrected oVEMP
To eliminate the effect of variations of muscle activities, amplitude (dimensionless) was employed for inter-
the mean background amplitude was calculated from aural comparisons.
Association of ACS oVEMP with cVEMP and caloric test 947

Percent cVEMP asymmetry = 100 |CAcr–CAcl|/ showed abnormal responses (Figure 2). Nine of
(CAcr+CAcl) (healthy subjects) the 11 patients showed absent cVEMP responses, and
Percent cVEMP asymmetry = 100 (CAcu–CAca)/ 2 showed prolonged p13 latencies. Concerning
(CAcu+CAca) (patients) responses on the unaffected side stimulation, two of
CAcr(l) = corrected amplitude of p13–n23 on the the nine patients showed absence of responses. Nine
right (left) patients showed decreased caloric responses (CP >
CAcu(a) = corrected amplitude of p13–n23 on the 20%). Table II shows the correlations of findings in
unaffected (affected) side one test to those in another test. Only the ACS oVEMP
|CAcr–CAcl| represented the absolute value of findings and caloric test findings showed a significant
CAcr–CAcl. association (p = 0.0045, Fisher’s exact probability test).
Table III shows the association between MD dis-
Caloric tests ease stage and the clinical test results. The MD
patients were classified into four stages according to
Caloric tests were performed using electronystagmo- hearing levels [13]. Patients with a hearing level within
graphy (ENG) by irrigating the external ear canal with 25 dB (average hearing levels of 500, 1000, and
cold water while the subject was in a dark room. CP in 2000 Hz) were classified into stage I. Stage II was
the caloric test was calculated using the maximum 26–40 dB, stage III was 41–70 dB, and stage IV was
slow phase eye velocity of caloric nystagmus. higher than 70 dB. Using these criteria, nine patients
were classified into stage I, six into stage II, and five
Results into stage III. The patients classified into stage I
showed normal results on all three tests or abnormal
Healthy subjects results on only one test. The patients classified into
stage II showed abnormal results on one or more
All seven control subjects showed ACS oVEMP and tests. The patients classified into stage III showed
ACS cVEMP responses on both sides. Both the ACS abnormal results on two tests or on all three tests.
oVEMP and ACS cVEMP showed significant corre-
lation of amplitudes (nI–pI and p13–n23) to the aver- VN patients
age background muscle activity (r = 0.695, p = 0.0045,
t test for oVEMP; r = 0.612, p = 0.018, t test for All six patients with unilateral VN showed abnormal
cVEMP). Therefore, we consider that the correction of ACS oVEMP responses after stimulation on the
amplitudes using the average background muscle activ- affected side (Figure 3). Five patients showed absence
ity is valid. The means (SDs) for healthy subjects are of oVEMP and one showed prolonged nI latency.
summarized in Table I. Based on these findings, we set Concerning ACS cVEMP, two patients showed
upper limits for the normal range (mean + 2 SD), abnormal (absent) cVEMPs. Canal pareses (%) of
which are also shown in Table I. VN patients were 59%, 65%, 74%, 75%, 78%, and
100%, respectively.
MD patients
Discussion
Among the 20 patients with unilateral definite MD,
9 showed abnormal ACS oVEMPs after stimulation of This study demonstrated that ACS cVEMP and ACS
the affected side. Eight of these patients showed absence oVEMP are independent of each other but that
of ACS oVEMP, and one showed decreased amplitudes. oVEMP results could have a significant association
Concerning responses on the unaffected side stimula- with caloric test results in MD patients. Similar dis-
tion, two of the eight patients showed absence of sociation between the results of these two tests was
responses. Concerning ACS cVEMP, 11 patients also reported by Huang et al. [7]. Taylor et al. [14]

Table I. oVEMP and cVEMP results of healthy subjects.

% oVEMP nI (oVEMP) pI (oVEMP) % cVEMP p13 (cVEMP) n23 (cVEMP)


Parameter asymmetry (ms) (ms) asymmetry (ms) (ms)

Mean 16.3 11.2 15.4 16.4 15.1 23.7


SD 14.0 1.2 1.3 12.6 1.3 1.8
Upper limit of normal 44.3 13.6 18.0 41.6 17.7 27.3
range (mean + SD)
948 T. Murofushi et al.

Right ear stim. Left ear stim.


n23
cVEMP

p13
200 µV
nl nl 10 ms
oVEMP

pl 2 µV
pl stim.
stim.
10 ms

Figure 2. cVEMP and oVEMP of a left MD patient (60-year-old woman, stage II). This patient showed absence of cVEMP on left ear
stimulation, but showed normal oVEMP on both sides.

also studied AC cVEMP and AC oVEMP. While Caloric tests are widely used as a clinical test of
they reported that prevalence of AC oVEMP and lateral semicircular canal function, while VEMP are
AC cVEMP abnormalities were not significantly dif- regarded as tests of otolith organ function. The pres-
ferent, they did not mention the relationships between ent study suggested that the oVEMP to ACS could
the results of two tests and disease stage in each reflect different functions from the cVEMP to ACS,
patient. Therefore, their results are not necessarily as indicated in previous reports [15]. To explain the
inconsistent with ours. In our study, the dissociation independence of the two types of VEMP tests, we
was clearer in the VN patients. should consider the hypothesis that ACS oVEMP
When the relations between disease stage of MD predominantly reflects utricular function while ACS
and test results were studied, patients in stage I did cVEMP predominantly reflects saccular function.
not show any abnormal results or had an abnormal A histopathological study showed that hydrops in
result on only one test, ACS cVEMP or ACS oVEMP, the saccule were observed in 6 of the 17 contralateral
especially ACS cVEMP. None of the patients showed ears (asymptomatic ears) (35%) of unilateral MD
abnormal caloric tests. The present study suggested patients while hydrops in the saccule were observed
that ACS cVEMP could be affected in the earlier stage in all the 17 ipsilateral ears (symptomatic ears) [16].
of MD, while ACS oVEMP and caloric test could be This study suggested that the saccule could be
affected in the later stages. affected at the early stage of the disease. The present
findings that ACS cVEMP tended to show abnormal
results at an earlier stage than other tests are consis-
Table II. Association between neuro-otological tests in patients tent with histopathological findings. Furthermore,
with Meniere’s disease. our results are basically consistent with those of a
preceding study into the relationships between MD
cVEMP

Normal Abnormal Total


Table III. Association of disease stages of Meniere’s disease with
oVEMP Normal 4 7 11
clinical test results.
Abnormal 5 4 9
Test results Stage I Stage II Stage III
Total 9 11 20
OOO 4 0 0
Caloric
OOX 0 0 0
Normal Abnormal OXO 4 2 0
oVEMP Normal 10 1 11 XOO 1 1 0
Abnormal 2 7 9 OXX 0 0 1
Total 12 8 20 XOX 0 1 2
XXO 0 0 0
Caloric
XXX 0 2 2
Normal Abnormal
Total 9 6 5
cVEMP Normal 6 3 9
O, normal result; X, abnormal result; left O(X), results of oVEMP;
Abnormal 6 5 11 middle O(X), results of cVEMP; right O(X), results of caloric tests
Total 12 8 20 (e.g. OXO = normal oVEMP and caloric response but abnormal
cVEMP).
Association of ACS oVEMP with cVEMP and caloric test 949

Right ear stim. Left ear stim.


n23
n23

cVEMP
p13 p13
100 µV
nl 10 ms

oVEMP
pl 2 µV
stim. stim.
10 ms

Figure 3. cVEMP and oVEMP of a left VN patient (77-year-old man, superior vestibular neuritis). This patient showed absent oVEMP on
stimulation of the left ear, but showed normal cVEMP on both sides.

stage and ACS cVEMP findings [17]. As the utricle Then, we must assess the validity of the current
and semicircular canals could be affected at a later hypothesis that oVEMP predominantly reflects utric-
stage, the results of ACS oVEMP and caloric tests ular functions while cVEMP predominantly reflects
might show a significant association. saccular functions from neurophysiological and neu-
The current hypothesis also explains the results in roanatomical perspectives.
patients with VN. It is known that VN could be Utricular inputs clearly evoke eye movements [20].
classified into three types; total, superior, and infe- According to Suzuki et al. [20], electrical stimulation
rior VN [2]. As the caloric test is a test of the superior of selective utricular afferents predominantly caused
vestibular nerve innervating the lateral semicircular activation of the ipsilateral superior oblique muscle
canal, inferior VN was overlooked when the diag- and the contralateral inferior oblique muscle. Activa-
nostic criteria for VN included decreased caloric tion of the contralateral inferior oblique muscle is
responses. Therefore, VN in this study was com- likely to lead to nI potentials of oVEMP below the
posed of total VN and superior VN. As utricular eye contralateral to the stimulated ear. However, the
afferents as well as lateral semicircular canal afferents sacculo-ocular reflex pathway is weak and remains
are in the superior vestibular nerve, the VN patients unclear, although there might be some polysynaptic
in this study should have abnormal ACS oVEMP reflex pathways [21]. Therefore, it is likely that ACS
irrespective of ACS cVEMP results. In fact all the oVEMP predominantly reflects utricular functions. In
VN patients in this study showed abnormal ACS studies using cats carried out by Sato et al. [22,23], it
oVEMP, while only two of the six showed abnormal was reported that among the vestibulo-spinal neurons
ACS cVEMP. (VSNs) receiving saccular inputs, 59% descend
Of course, we need to consider alternative explana- through the medial vestibulo-spinal tract (MVST),
tions for the independence of the ACS oVEMP find- which contains the cVEMP pathway [2]. Among the
ings and ACS cVEMP findings. Some investigators VSNs receiving utricular inputs, however, only 12%
proposed the hypothesis that ACS oVEMP are evoked descend through the MVST. These findings suggest
by saccular stimulation. Govender et al. [18] pro- that cVEMP might dominantly reflect saccular inputs.
posed that the dissociation of ACS oVEMP findings Finally, we need to validate the sensitivity of utric-
and ACS cVEMP findings in VN patients might be ular afferents to ACS in mammals. Murofushi and
caused by disorders of saccular afferents in the super- Curthoys [24] reported that sound-sensitive vestibu-
ior vestibular nerve, which arise from the antero- lar afferents exist in the caudal part of the superior
superior part of the saccule. While this hypothesis vestibular nerve as well as the inferior vestibular nerve
could explain the dissociation in the VN patients, it is in guinea pigs. Although the authors suggested that
hard to explain the dissociation in the MD patients, this finding resulted from the existence of saccular
because the lesion site of MD is not in the vestibular afferents in the superior vestibular nerve, it could
nerve but in the inner ear. Colebatch [19] proposed result from sound-sensitive utricular afferents. As
that facilitation of saccular afferents by utricular affer- the utricular macula as well as the saccular macula
ents is required to produce ACS oVEMP. Also, this is located close to the footplate of the stapes [25],
hypothesis does not explain our present results that utricular afferents might respond to ACS. Sensitivity
many MD patients showed abnormal ACS cVEMP of utricular afferents to ACS should be proven more
but normal ACS oVEMP. clearly in future studies.
950 T. Murofushi et al.

In conclusion, our study concerning the associa- [10] AAO-HNS guidelines for the evaluation of therapy in
tion of ACS oVEMP findings with cVEMP and calo- Meniere’s disease. Otolaryngol Head Neck Surg 1995;113:
181–5.
ric testing demonstrated the independence of ACS [11] Murofushi T, Halmagyi GM, Yavor RA, Colebatch JG.
oVEMP from ACS cVEMP. However, the ACS Absent vestibular evoked potentials in vestibular neurolabyr-
oVEMP findings did show an association with find- inthitis; an indicator of involvement of the inferior vestibular
ings from caloric testing. These findings support the nerve? Arch Otolaryngol Head Neck Surg 1996;122:845–8.
hypothesis that findings on ACS oVEMP predomi- [12] Karino S, Ito K, Ochiai A, Murofushi T. Independent effects
of simultaneous inputs from the saccule and lateral semicir-
nantly reflect utricular functions, while those of ACS cular canal. Evaluation using VEMPs. Clin Neurophysiol
cVEMP predominantly reflect saccular functions. 2005;116:1707–15.
Furthermore, we showed that this hypothesis is also [13] Murofushi T, Matsuzaki M, Takegoshi H. Glycerol affects
likely from both neurophysiological and neuroana- vestibular evoked myogenic potentials in Meniere’s disease.
Auris Nasus Larynx 2001;28:205–8.
tomical perspectives. However, we need to exclude
[14] Taylor R, Wijewardene AA, Gibson WPR, Black DA,
the possibility of contribution of the lateral semicir- Halmagyi GM, Welgampola MS. The vestibular evoked-
cular canal to ACS oVEMP. potential profile of Meniere’s disease. Clin Neurophysiol
2010; Dec 16 [Epub ahead of print].
Declaration of interest: The authors report no [15] Murofushi T, Wakayama K, Chihara Y. oVEMP to air-
conducted tones reflects functions of different vestibular
conflicts of interest. The authors alone are responsible
populations from cVEMP. Eur Arch Otorhinolaryngol
for the content and writing of the paper. 2010;267:995–6.
[16] Lin MY, Timmer FCA, Oriel BS, Zhou G, Guinan JJ,
References Kujawa SG, et al. Vestibular evoked myogenic potentials
(VEMP) can detect asymptomatic saccular hydrops. Laryn-
[1] Colebatch JG, Halmagyi GM, Skuse NF. Myogenic poten- goscope 2006;116:987–92.
tials generated by a click-evoked vestibulocollic reflex. [17] Young YH, Huang TW, Cheng PW. Assessing the stage of
J Neurol Neurosurg Psychiatry 1994;57:190–7. Meniere’s disease using vestibular evoked myogenic poten-
[2] Murofushi T, Kaga K. 2009. Vestibular evoked myogenic tials. Arch Otolaryngol Head Neck Surg 2003;129:815–18.
potential. Tokyo: Springer. [18] Govender S, Rosengren SM, Colebatch JG. Vestibular neu-
[3] Todd NP, Rosengren SM, Aw ST, Colebatch JG. Ocular ritis has selective effects on air- and bone-conducted cervical
vestibular evoked myogenic potentials (OVEMPs) produced and ocular vestibular evoked myogenic potentials. Clin Neu-
by air- and bone-conducted sound. Clin Neurophysiol 2007; rophysiol 2011; Jan 14 [Epub ahead of print].
118:381–90. [19] Colebatch JG. Sound conclusion? Clin Neurophysiol 2010;
[4] Chihara Y, Ushio M, Iwasaki S, Murofushi T. Vestibular- 121:124–6.
evoked extraocular potentials by air-conducted sound: [20] Suzuki JI, Tokumasu K, Goto K. Eye movements from single
another clinical test of the vestibular function. Clin Neuro- utricular nerve stimulation in the cat. Acta Otolaryngol 1969;
physiol 2007;118:2745–51. 68:350–62.
[5] Iwasaki S, McGarvie LA, Halmagyi GM, Burgess AM, [21] Isu N, Graf W, Sato H, Kushiro K, Zakir M,
Kim J, Colebatch JG, et al. Head taps evoke a crossed Imagawa M, et al. Sacculo-ocular reflex connectivity in
vestibulo-ocular reflex. Neurology 2007;68:1227–9. cats. Exp Brain Res 2000;131:262–8.
[6] Rosengren SM, Todd NPM, Colebatch JG. Vestibular-evoked [22] Sato H, Endo K, Ikegami H, Imagawa M, Sasaki M,
extraocular potentials produced by stimulation with bone- Uchino Y. Properties of utricular nerve-activated vestibu-
conducted sound. Clin Neurophysiol 2005;116:1938–48. lospinal neurons in cats. Exp Brain Res 1996;112:
[7] Huang CH, Wang SJ, Young YH. Localization and preva- 197–202.
lence of hydrops formation in Meniere’s disease using a test [23] Sato H, Imagawa M, Isu N, Uchino Y. Properties of saccular
battery. Audiol Neurotol 2011;16:41–8. nerve-activated vestibulospinal neurons in cats. Exp Brain
[8] Curthoys IS, Iwasaki S, Chihara Y, Ushio M, McGarvie LA, Res 1997;116:381–8.
Burgess AM. The ocular vestibular-evoked myogenic poten- [24] Murofushi T, Curthoys IS. Physiological and anatomical
tial to air-conducted sound; probable superior vestibular study of click-sensitive primary vestibular afferents in the
nerve origin. Clin Neurophysiol 2011;122:611–16. guinea pig. Acta Otolaryngol 1997;117:66–72.
[9] Murofushi T, Monobe H, Ozeki H, Ochiai A. The site of [25] Uzun-Coruhlu H, Curthoys IS, Jones AS. Attachment of the
lesions in “vestibular neuritis”; study by galvanic VEMP. utricular and saccular maculae to the temporal bone. Hear
Neurology 2003;61:417–18. Res 2007;233:77–85.
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