Clinical Neurophysiology xxx (2014) xxx–xxx
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Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing Chisato Fujimoto ⇑, Naoya Egami, Makoto Kinoshita, Keiko Sugasawa, Tatsuya Yamasoba, Shinichi Iwasaki Department of Otolaryngology, Faculty of Medicine, The University of Tokyo, Japan
a r t i c l e
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Article history: Accepted 9 July 2014 Available online xxxx Keywords: Evoked potentials Hearing loss Vertigo Vestibular function tests
h i g h l i g h t s We investigated the extent of vestibular lesions in idiopathic sudden hearing loss (ISHL) with vertigo
using cervical and ocular vestibular evoked myogenic potential (cVEMP, oVEMP) testing and caloric testing. The percentage of abnormal responses in patients with ISHL with vertigo was highest in the cVEMP test, followed by the oVEMP and caloric tests. The vestibular end organs closest to the cochlea tended to be preferentially affected in ISHL with vertigo.
a b s t r a c t Objective: To investigate the extent of vestibular lesions in idiopathic sudden hearing loss (ISHL) with vertigo. Method: We reviewed the clinical records of 25 consecutive new patients with ISHL with vertigo. We classified patients based on their pattern of vestibular dysfunction. All patients showed cochlear damage and were labeled C (cochlear) type. If a patient showed abnormal cervical vestibular evoked myogenic potential (cVEMP), ocular VEMP (oVEMP) or caloric responses, an S (saccule), U (utricule) or L (lateral semicircular canal) respectively was added to their label. Results: All patients underwent cVEMPs and caloric tests. Sixteen (64%) and 13 (52%) showed abnormal cVEMPs and caloric responses, respectively, on the affected side. Among the 23 patients who underwent oVEMPs, 10 (43%) showed abnormal oVEMPs on the affected side. Of these 23 patients, 6 (26%) were classified as C type, 4 (17%) as CS type, 1 (4%) as CL type, 1 (4%) as CSU type, 2 (9%) as CSL type, 1 (4%) as CUL type, 8 (35%) as CSUL type. Conclusion: The vestibular end organs close to the cochlea tended to be preferentially affected. Significance: It is likely that vestibular dysfunction extends from organs close to the cochlea to those further from the cochlea. Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Idiopathic sudden hearing loss (ISHL) is clinically defined as a severe sensorineural hearing loss of sudden onset with unknown
⇑ Corresponding author. Address: Department of Otolaryngology, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan. Tel.: +81 3 5800 8665; fax: +81 3 3814 9486. E-mail address: [email protected] (C. Fujimoto).
cause. Different pathogeneses of sudden hearing loss such as viral infection, vascular obstruction, and cochlear membrane breaks have been proposed (Gussen, 1976; Schuknecht and Donovan, 1986; Schuknecht et al., 1973; Simmons, 1968). Approximately 40% of patients with ISHL also suffer from vestibular symptoms (Nakashima and Yanagita, 1993; Shaia and Sheehy, 1976), which may occur at the onset of hearing loss or be delayed for hours or even days. Vertigo appears more frequently in association with profound hearing loss and the recovery of hearing is worse in patients with vertigo than those without vertigo (Mattox and
http://dx.doi.org/10.1016/j.clinph.2014.07.028 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
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C. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
Simmons, 1977; Nakashima and Yanagita, 1993; Shaia and Sheehy, 1976; Wilson et al., 1982). As for the findings of vestibular function testing in ISHL with vertigo, it has previously been reported that 40% of patients show reduced caloric responses in the affected ear (Iwasaki et al., 2005b; Mattox and Simmons, 1977; Shaia and Sheehy, 1976; Wilson et al., 1982). Caloric testing has been used to clinically assess the lateral semicircular canal and superior vestibular nerve. On the other hand, cervical vestibular evoked myogenic potentials (cVEMPs), recorded from the sternocleidomastoid muscle (SCM) in response to brief pulses of air-conducted sound (ACS), bone-conducted vibration (BCV) or electrical stimulation (Colebatch and Halmagyi, 1992; Halmagyi et al., 1995; Watson et al., 1998), have been used as a clinical test of the saccule and inferior vestibular nerve. Clinical and neurophysiological studies have suggested that cVEMPs to ACS are generated by the activation of saccular afferents (Colebatch et al., 1994; Murofushi and Curthoys, 1997; Murofushi et al., 1995, 1996a,b). Using these vestibular function tests to detect peripheral vestibular dysfunction, our group previously demonstrated that in patients with ISHL with vertigo, the saccule was more frequently involved than the semicircular canals (Iwasaki et al., 2005b). This result was consistent with previous histopathological case studies showing that atrophic changes of the saccular macula were most frequently observed in the vestibular organs of patients with ISHL (Gussen, 1976; Inagaki et al., 2012; Ishii and Toriyama, 1977; Sando et al., 1977; Schuknecht and Donovan, 1986; Yoon et al., 1990). Recently, it has been revealed that short-latency potentials called ocular VEMPs (oVEMPs) can be recorded from beneath the eyes in response to ACS and BCV (Iwasaki et al., 2007; Rosengren et al., 2005). oVEMPs are considered to reflect activity of the inferior oblique muscle and represent vestibular function mediated by a crossed otolith-ocular pathway (Chihara et al., 2007; Iwasaki et al., 2007, 2008; Rosengren et al., 2005; Todd et al., 2007; Weber et al., 2012). oVEMPs mainly reflect the function of the utricle and the superior vestibular nerve (Curthoys et al., 2006, 2011; Iwasaki et al., 2009, 2010). Combined use of cVEMP, oVEMP and caloric tests facilitates a more precise and comprehensive examination of the nervous system. In the present study, we investigated the extent of vestibular lesions in patients with ISHL with vertigo using cVEMP, oVEMP and caloric testing. Furthermore, we evaluated the relationship between the severity of hearing loss and the extent of vestibular dysfunction. 2. Materials and methods 2.1. Study design This retrospective data collection study was approved by the regional ethical standards committee in the Faculty of Medicine at the University of Tokyo and was conducted according to the tenets of the Declaration of Helsinki. 2.2. Subjects We reviewed the clinical records of consecutive new patients with ISHL with vertigo visiting the Balance Disorder Clinic at the University of Tokyo Hospital between January 2008 and December 2012. All of these patients had undergone a detailed history-taking and a battery of tests including a physical examination and standardized neurological, neuro-otological, neuro-ophthalmological and audiological examinations. Eye movements were observed using an infrared charge-coupled device camera and recorded by electronystagmography.
The diagnostic criteria for ISHL with vertigo included a sensorineural hearing loss of more than 30 dB, occurring in at least 3 contiguous frequencies in less than 3 days (Stachler et al., 2012; Wilson et al., 1980), a single attack of vertigo occurring almost simultaneously with the onset of hearing loss, and the absence of other neurological signs. Those patients who had multiple attacks of hearing loss and vertigo were excluded from this study to rule out Mèniére’s disease or migraine. When the cause of SHL and vertigo was unknown, ISHL was considered. In this study, 25 patients with ISHL with vertigo were included [15 men, 10 women, mean (±SD) age 63.6 (±13.6) years, range 20–88]. 2.3. Caloric testing Caloric testing was performed by irrigating the external auditory canal with 2 ml ice water (4 °C) for 20 s followed by aspiration of water. This method of caloric stimulation is easier to perform than bithermal irrigation with water at 30 and 44 °C, and has been shown to have a high sensitivity and specificity for detecting canal paresis (CP) based on Jongkee’s formula (Schmal et al., 2005). Caloric nystagmus was recorded, in a darkened room, using an electronystagmograph. We defined an abnormal caloric response by either of the following criteria: (1) CP percentage >20% (Iwasaki et al., 2005a); (2) maximum slow phase eye velocity 150 lV) were not enrolled in the present study. We were not able to calculate the corrected amplitude for cVEMPs as we did not measure the rectified background activity of the SCMs during the recordings. When no reproducible p13–n23 was present in 2 runs, we regarded it as an ‘‘absent response’’. When a reproducible p13– n23 was present and cVEMP AR (%) was greater than the normal upper limits, we regarded it as a ‘‘decreased response’’. 2.5. oVEMP testing Subjects lay supine on a bed, with their head supported by a pillow and with surface EMG electrodes placed on the skin 1 cm below (active) and 3 cm below (indifferent) the center of each lower eyelid. The ground electrode was placed on the chin. During testing, the subject looked up approximately 30 degrees above
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
C. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
straight ahead and maintained their focus on a small dot approximately 1 m from their eyes. The signals were amplified by a differential amplifier (bandwidth: 0.5–500 Hz), and the unrectified signals were averaged (n = 50) using Neuropack R. The BCV stimuli were 4 ms tone-bursts of 500 Hz vibration (rise/fall time = 1 ms and plateau time = 2 ms) delivered by a hand-held 4810 mini-shaker (Bruel and Kjaer, Naerum, Denmark) fitted with a short rod terminated in a bakelite cap 1.5 cm in diameter, which was placed perpendicularly on the forehead at the hairline, in the midline (Fz). The driving voltage was 80 V peak to peak, and it produced a peak force level of 128 dB re 1 lN. The stimuli were applied 3 times per second, and the time window for analysis was 50 ms. Averages of two sets of 50 stimuli each were computed. Consecutive runs were performed to confirm the reproducibility of the oVEMP responses. We analyzed the first negative peak (nI) latency, the subsequent positive peak (pI) latency, and the amplitude between nI and pI. Amplitude and latency were determined from the average of 2 runs. For the evaluation of amplitude, the asymmetry ratio for nI–pI amplitude (oVEMP AR) was calculated as 100 [(Au Aa)/(Aa + Au)], where Au is the nI–pI amplitude on the unaffected side and Aa is the nI–pI amplitude on the affected side (Chihara et al., 2007). Responses recorded from the eye contralateral to stimulation were used for calculating oVEMP AR. On the basis of the results from normal subjects, the upper limit of normal oVEMP AR was set at 27.3 for oVEMPs to BCV (Iwasaki et al., 2008). When no reproducible nI–pI was present in 2 runs, we regarded it as an ‘‘absent response’’. When a reproducible nI–pI was present and the oVEMP AR (%) was greater than the normal upper limits, we regarded it as a ‘‘decreased response’’.
2.6. Pure tone audiogram Pure tone audiograms were categorized as high- or low-tone hearing loss, flat-type hearing loss, or profound hearing loss. The group with high-tone hearing loss was defined as those patients with an average loss of 4–8 kHz, surpassing the average of 0.25– 0.5 kHz by 30 dB or more. The low-tone hearing loss group demonstrated an average loss of 0.25–0.5 kHz, surpassing the average of 4–8 kHz by 30 dB or more. The flat-type group consisted of patients with a difference between the worst and best hearing levels of 20 dB or less among 6 frequencies: 0.25, 0.5, 1, 2, 4, and 8 kHz. In the group with profound hearing loss, at least 2 frequencies produced results that were off the scale, and the difference between the hearing level and the maximum sound level generated by the audiometer was within 10 dB at all 6 frequencies. The pure tone average (PTA) was calculated with thresholds at 0.5, 1 and 2 kHz.
2.7. Classification of patients We classified patients based on their pattern of vestibular dysfunction. All the patients showed cochlear damage and were labeled C (cochlear) type. If a patient showed abnormal cVEMP, oVEMP or caloric responses, we added an S (saccule), U (utricule) or L (lateral semicircular canal), respectively. For example, if a patient showed abnormal cVEMPs and oVEMPs but normal caloric responses, we classified the patient as a CSU type.
2.8. Statistical analysis The comparison of the PTA between patients with and without an abnormal caloric response was statistically analyzed using the Student’s t-test (p < 0.05). IBM SPSS statistics 21 (IBM Corporation, New York, United States) was used for the statistical analysis.
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3. Results The clinical characteristics of the patients are presented in Table 1. Of the 25 included patients, the right ear was involved in 12 patients (48%), and the left ear was involved in 13 patients (52%). None of the patients showed clear findings of conductive hearing loss; the outer ear and tympanum were assessed, and tympanometry was performed. The audiogram types of the 25 patients were as follows: high-tone hearing loss in 6 (24%), profound hearing loss in 6 (24%), flat-type hearing loss in 13 (52%). There were no patients with low-tone hearing loss. Twenty of the 25 patients (80%) showed spontaneous nystagmus. Among them, 14 patients (70%) showed horizontal nystagmus whereas 6 patients (30%) showed horizontal–torsional nystagmus. Four of the 5 patients (80%) who did not have spontaneous nystagmus had normal responses in both cVEMP and caloric tests. Twenty-three of the 25 patients underwent cVEMP, oVEMP and caloric testing, while the other 2 patients underwent cVEMP and caloric testing, but not oVEMP testing. Among the 25 patients who underwent cVEMP and caloric tests, 16 (64%) showed abnormal cVEMP responses on the affected side and 13 patients (52%) showed abnormal caloric responses on the affected side. Among the 23 patients who underwent oVEMP testing, 10 (43%) showed abnormal oVEMPs on the affected side. The percentage of abnormal responses in patients with ISHL with vertigo was the highest in cVEMP testing. Of the 23 patients who underwent cVEMP, oVEMP and caloric tests, 6 (26%) were classified as C type; 4 (17%) as CS type; 1 (4%) as CL type; 1 (4%) as CSU type; 2 (9%) as CSL type; 1 (4%) as CUL type; 8 (35%) as CSUL type (Fig. 1). No patients were classified as CU type. Table 2 shows the audiometric characteristics in each type of vestibular dysfunction. For investigating the association of the severity of hearing loss with the extent of vestibular dysfunction, a comparison of the PTA between the patients with and without an abnormal caloric response was statistically analyzed. The average PTA was larger in patients with abnormal caloric responses (83.8 dB) than those without abnormal caloric responses (74.3 dB). However, no statistical difference was found (p > 0.05). In patients with profound hearing loss, the percentage of patients with abnormal caloric responses (31%) was larger than those without abnormal caloric responses (17%).
4. Discussion In the present study, we have examined vestibular function in ISHL patients with vertigo using cVEMP, oVEMP and caloric testing. Caloric testing has been used clinically as a test of the lateral semicircular canal and superior vestibular nerve. cVEMPs have been used clinically as a test of the saccule and inferior vestibular nerve (Colebatch et al., 1994; Murofushi et al., 1996b, 1998), although some recent studies have shown involvement of vestibular end organs other than the saccule for generating cVEMPs (Wei et al., 2013; Zhu et al., 2011). oVEMPs have been mainly regarded as a test of the utricle and the superior vestibular nerve (Curthoys et al., 2006, 2011; Iwasaki et al., 2009, 2010), although the origin of the response to ACS remains controversial (Chihara et al., 2007; Curthoys et al., 2011). Using these vestibular function tests, we showed that the percentage of abnormal responses in patients with ISHL with vertigo was highest in the cVEMP test, followed by the oVEMP and caloric tests. Our group has previously demonstrated using cVEMP and caloric testing that the saccule is more frequently damaged than the semicircular canals in patients with ISHL with vertigo (Iwasaki et al., 2005b). Previous histopathological case studies
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
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Table 1 Clinical characteristics of each patient with ISHL with vertigo. Patient no./gender/age
Side
PTA
Type of audiogram
Nystagmus
cVEMP burst
oVEMP BCV
Caloric test
Type of dysfunction
1/M/61 2/M/65 3/F/76 4/M/64 5/F/69 6/M/62 7/M/60 8/F/67 9/F/71 10/F/62 11/M/44 12/M/74 13/M/63 14/M/66 15/M/39 16/F/65 17/M/79 18/M/57 19/M/63 20/F/59 21/F/20 22/M/76 23/M/66 24/F/75 25/F/88
Rt. Lt. Lt. Rt. Lt. Rt. Lt. Lt. Rt. Lt. Lt. Rt. Rt. Lt. Rt. Lt. Lt. Rt. Lt. Lt. Lt. Rt. Lt. Rt. Rt.
26.7 90 66.7 91.7 96.7 105 18.3 83.3 60 115 101.7 60 56.7 63.3 111.7 66.7 45 58.3 73.3 96.7 110 115 115 78.3 76.7
High-tone High-tone Flat-type Flat-type Flat-type Profound High-tone Flat-type Flat-type Profound Flat-type Flat-type High-tone Flat-type Profound High-tone Flat-type Flat-type Flat-type Flat-type Profound Profound Profound Flat type High-tone
No Horizontal–torsional Horizontal No Horizontal No Horizontal Horizontal Horizontal Horizontal Horizontal–torsional Horizontal Horizontal Horizontal Horizontal Horizontal No Horizontal Horizontal Horizontal–torsional Horizontal Horizontal–torsional Horizontal–torsional No Horizontal–torsional
Normal Normal Normal Normal Normal Normal Lt. absence Lt. absence R5d4t. 38.9 Lt. absence Normal Rt. absence Rt. absence Lt. absence Normal Lt. absence Lt. absence Rt. absence Lt. absence Lt. absence Lt. 35.1 Bil. absence Lt. absence Normal Bil. absence
Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Rt. absence Normal Normal Rt. absence Lt. absence Bil. absence Rt. 44.8 Lt. 32.8 Lt. 64.9 Lt. absence Rt. absence Lt. absence N/A N/A
Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Lt. CP 100% Normal Rt. CP33% Lt. CP 36% Rt. CP41% Lt. CP 71% Lt. CP 28% Rt. CP100% Lt. CP 31% Lt. CP 66% Lt. CP 100% Rt. CP68% Lt. CP 64% Normal Rt. CP76%
C C C C C C CS CS CS CS CL CSU CSL CSL CUL CSUL CSUL CSUL CSUL CSUL CSUL CSUL CSUL N/A N/A
ISHL = idiopathic sudden hearing loss, PTA = pure tone average, cVEMP = cervical vestibular evoked myogenic potential, oVEMP = ocular vestibular evoked myogenic potential, BCV = bone-conducted vibration, M = male, F = female, Lt. = left, Rt. = right, N/A = not applicable, CP = canal paresis, AR = asymmetry ratio for p13–n23 or nI–pI amplitude.
Fig. 1. Percentage of C, CS, CU, CL, CSU, CSL, CUL and CSUL types in patients with ISHL with vertigo, and representative data from vestibular tests in a patient of the C, CSU and CSUL types. The C type patient was a 64-year-old male with right ISHL with vertigo who showed normal caloric, cVEMP and oVEMP responses. The CSU type patient was a 74year-old male with right ISHL with vertigo who showed no cVEMP responses on the right side and no oVEMP responses on the left side in the presence of caloric responses. The CSUL type patient was a 44-year-old male with left ISHL with vertigo who showed no cVEMP responses on the left side, abnormal oVEMP responses on the right side and no caloric responses on the left side. cVEMP = cervical vestibular evoked myogenic potential, oVEMP = ocular VEMP, M = male, Rt. = right, Lt. = left, C = cochlear, S = saccule, U = utricle, L = lateral semicircular canal. The black arrowhead shows p13 for cVEMPs or nI for oVEMPs. The white arrowhead shows n23 for cVEMPs or pI for oVEMPs. The horizontal scale bar shows 10 ms for both cVEMPs and oVEMPs. The vertical scale bar shows 100 lV for cVEMPs or 2 lV for oVEMPs.
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
C. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx Table 2 Audiometric characteristics in each type of vestibular dysfunction in ISHL with vertigo. Type of dysfunction
Number
Median of pure tone average (dB)
Percentage of profound hearing loss (number)
C CS CL CSU CSL CUL CSUL
6 4 1 1 2 1 8
90.9 71.7 101.7 60 60 63.3 85
17% (1) 25% (1) 0% (0) 0% (0) 0% (0) 100% (1) 38% (3)
(26%) (17%) (4%) (4%) (9%) (4%) (35%)
ISHL = idiopathic sudden hearing L = lateral semicircular canal.
loss,
C = cochlear,
S = saccule,
U = utricle,
have reported that atrophy of the saccular macula was most frequently observed in the vestibular organs of patients with ISHL (Gussen, 1976; Inagaki et al., 2012; Ishii and Toriyama, 1977; Sando et al., 1977; Schuknecht and Donovan, 1986; Yoon et al., 1990). The result of the present study is consistent with these previous reports. Patients were classified into C, CS, CSU, CSL or CSUL types; 91% of them belonged to the C, CS, CSU or CSUL type. No patients were classified into the CU, CUL or CL type. These results suggest that the vestibular end organs closest to the cochlea tend to be preferentially affected in ISHL with vertigo. Vestibular dysfunction in ISHL with vertigo may extend from organs close to the cochlea to those further from the cochlea. It has been considered that viral infection is one of the probable causes of ISHL. A previous report indicated that the inner ear pathologies of known viral labyrinthitis cases such as mumps and rubella are similar to that in ISHL (Schuknecht and Donovan, 1986). Microscopic studies of the temporal bones showed that the loss of vestibular hair cells in patients with ISHL was most frequently observed in the saccule but less so in the utricle and semicircular canals, as shown in patients with rubella (Alford, 1968; Lindsay et al., 1953; Schuknecht and Donovan, 1986). Vascular insults have been proposed as another cause of ISHL. In a previous study of the pathophysiology of labyrinthine infarction, the cochlea and the cristae of the anterior and horizontal semicircular canals developed degenerative changes while the utricular macula and the posterior canal ampulla and saccular macula were relatively preserved (Kim et al., 1999). This study proposed that a partial sparing of the inferior vestibular labyrinth may indicate a decreased vulnerability to ischemia because of its better collateral blood supply (Kim et al., 1999). The pattern of the extent of vestibular lesions in our study is similar to the results of vestibular damage in previous temporal bone studies of viral labyrinthitis. Our group have previously reported that the percentage of profound hearing loss was larger in the group which showed abnormal responses in both caloric and cVEMP tests compared with groups which showed normal responses in at least one of these tests (Iwasaki et al., 2005b). In the present study, the average PTA on the affected side and the percentage of profound hearing loss were both larger in patients with abnormal caloric responses than those without abnormal caloric responses. Taken together, it is likely that the more severe the hearing loss is, the more extensive the vestibular lesion might be. However, the number of patients in this study is small and the variance in the PTA in each type seems large. Further investigation using other data sets would be beneficial. This study has several limitations. First, being a retrospective data collection study there is the potential for both selection bias and information bias. Next, the functions of the anterior and posterior semicircular canals were not evaluated in this study. Those patients who were classified into the C type might have also had dysfunction of the anterior and posterior semicircular canals, while
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it is possible that the function of the saccule, the utricle and/or the lateral semicircular canal might have recovered before performing vestibular function tests. In addition, we did not examine any patients with ISHL without vertigo in this study. A previous report described the association between hearing loss and saccular dysfunction in older individuals, although the report did not mention if their patients had symptoms of vestibular dysfunction (Zuniga et al., 2012). We are not sure about whether our findings are specific to the patients exhibiting vertigo. In conclusion, the percentage of abnormal responses in patients with ISHL with vertigo was highest in the cVEMP test, followed by the oVEMP and caloric tests. Most of the patients were classified into C, CS, CSU or CSUL types. These results suggest that the vestibular end organs closest to the cochlea tend to be preferentially affected in ISHL with vertigo. Postural instability in peripheral vestibulopathy associated with abnormal responses in both caloric and cVEMP tests are more severe than when only one of the two tests is abnormal (Fujimoto et al., 2010). Evaluating the extent of vestibular lesions involved in ISHL may be useful for the prognostic prediction of postural stability and help improve the clinical strategy for vestibular rehabilitation practice. Acknowledgement This work was supported by grants from the Ministry of Education, Culture, Sports, Science & Technology in Japan to Chisato Fujimoto. Conflict of interest: None of the authors have potential conflicts of interest to be disclosed. References Alford BR. Rubella-la bete noire de la medecine. Laryngoscope 1968;78:1623–59. Chihara Y, Iwasaki S, Ushio M, Murofushi T. Vestibular-evoked extraocular potentials by air-conducted sound: another clinical test for vestibular function. Clin Neurophysiol 2007;118:2745–51. Colebatch JG, Halmagyi GM. Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 1992;42:1635–6. Colebatch JG, Halmagyi GM, Skuse NF. Myogenic potentials generated by a clickevoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 1994;57:190–7. Curthoys IS, Iwasaki S, Chihara Y, Ushio M, McGarvie LA, Burgess AM. The ocular vestibular-evoked myogenic potential to air-conducted sound; probable superior vestibular nerve origin. Clin Neurophysiol 2011;122:611–6. Curthoys IS, Kim J, McPhedran SK, Camp AJ. Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig. Exp Brain Res 2006;175:256–67. Fujimoto C, Murofushi T, Chihara Y, Suzuki M, Yamasoba T, Iwasaki S. Novel subtype of idiopathic bilateral vestibulopathy: bilateral absence of vestibular evoked myogenic potentials in the presence of normal caloric responses. J Neurol 2009;256:1488–92. Fujimoto C, Murofushi T, Chihara Y, Ushio M, Yamaguchi T, Yamasoba T, Iwasaki S. Effects of unilateral dysfunction of the inferior vestibular nerve system on postural stability. Clin Neurophysiol 2010;121:1279–84. Gussen R. Sudden deafness of vascular origin: a human temporal bone study. Ann Otol Rhinol Laryngol 1976;85:94–100. Halmagyi GM, Yavor RA, Colebatch JG. Tapping the head activates the vestibular system: a new use for the clinical reflex hammer. Neurology 1995;45:1927–9. Inagaki T, Cureoglu S, Morita N, Terao K, Sato T, Suzuki M, et al. Vestibular system changes in sudden deafness with and without vertigo: a human temporal bone study. Otol Neurotol 2012;33:1151–5. Ishii T, Toriyama M. Sudden deafness with severe loss of cochlear neurons. Ann Otol Rhinol Laryngol 1977;86:541–7. Iwasaki S, Chihara Y, Smulders YE, Burgess AM, Halmagyi GM, Curthoys IS, et al. The role of the superior vestibular nerve in generating ocular vestibular-evoked myogenic potentials to bone conducted vibration at Fz. Clin Neurophysiol 2009;120:588–93. Iwasaki S, McGarvie LA, Halmagyi GM, Burgess AM, Kim J, Colebatch JG, et al. Head taps evoke a crossed vestibulo-ocular reflex. Neurology 2007;68:1227–9. Iwasaki S, Murofushi T, Chihara Y, Ushio M, Suzuki M, Curthoys IS, et al. Ocular vestibular evoked myogenic potentials to bone-conducted vibration in vestibular schwannomas. Otol Neurotol 2010;31:147–52. Iwasaki S, Smulders YE, Burgess AM, McGarvie LA, Macdougall HG, Halmagyi GM, et al. Ocular vestibular evoked myogenic potentials in response to boneconducted vibration of the midline forehead at Fz. A new indicator of unilateral otolithic loss. Audiol Neurootol 2008;13:396–404.
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
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Iwasaki S, Takai Y, Ito K, Murofushi T. Abnormal vestibular evoked myogenic potentials in the presence of normal caloric responses. Otol Neurotol 2005a;26:1196–9. Iwasaki S, Takai Y, Ozeki H, Ito K, Karino S, Murofushi T. Extent of lesions in idiopathic sudden hearing loss with vertigo: study using click and galvanic vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 2005b;131:857–62. Kim JS, Lopez I, DiPatre PL, Liu F, Ishiyama A, Baloh RW. Internal auditory artery infarction: clinicopathologic correlation. Neurology 1999;52:40–4. Lindsay JR, Caruthers DG, Hemenway WG, Harrison S. Inner ear pathology following maternal rubella. Ann Otol Rhinol Laryngol 1953;62:1201–18. Mattox DE, Simmons FB. Natural history of sudden sensorineural hearing loss. Ann Otol Rhinol Laryngol 1977;86:463–80. Murofushi T, Curthoys IS. Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig. Acta Otolaryngol 1997;117:66–72. Murofushi T, Curthoys IS, Gilchrist DP. Response of guinea pig vestibular nucleus neurons to clicks. Exp Brain Res 1996a;111:149–52. Murofushi T, Curthoys IS, Topple AN, Colebatch JG, Halmagyi GM. Responses of guinea pig primary vestibular neurons to clicks. Exp Brain Res 1995; 103:174–8. Murofushi T, Halmagyi GM, Yavor RA, Colebatch JG. Absent vestibular evoked myogenic potentials in vestibular neurolabyrinthitis. An indicator of inferior vestibular nerve involvement? Arch Otolaryngol Head Neck Surg 1996b;122:845–8. Murofushi T, Matsuzaki M, Mizuno M. Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 1998;124:509–12. Murofushi T, Matsuzaki M, Wu CH. Short tone burst-evoked myogenic potentials on the sternocleidomastoid muscle: are these potentials also of vestibular origin? Arch Otolaryngol Head Neck Surg 1999;125:660–4. Nakashima T, Yanagita N. Outcome of sudden deafness with and without vertigo. Laryngoscope 1993;103:1145–9. Rosengren SM, McAngus Todd NP, Colebatch JG. Vestibular-evoked extraocular potentials produced by stimulation with bone-conducted sound. Clin Neurophysiol 2005;116:1938–48. Sando I, Loehr A, Harada T, Sobel JH. Sudden deafness: histopathologic correlation in temporal bone. Ann Otol Rhinol Laryngol 1977;86:269–79. Schmal F, Lubben B, Weiberg K, Stoll W. The minimal ice water caloric test compared with established vestibular caloric test procedures. J Vestib Res 2005;15:215–24.
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Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
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Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing Chisato Fujimoto ⇑, Naoya Egami, Makoto Kinoshita, Keiko Sugasawa, Tatsuya Yamasoba, Shinichi Iwasaki Department of Otolaryngology, Faculty of Medicine, The University of Tokyo, Japan
a r t i c l e
i n f o
Article history: Accepted 9 July 2014 Available online xxxx Keywords: Evoked potentials Hearing loss Vertigo Vestibular function tests
h i g h l i g h t s We investigated the extent of vestibular lesions in idiopathic sudden hearing loss (ISHL) with vertigo
using cervical and ocular vestibular evoked myogenic potential (cVEMP, oVEMP) testing and caloric testing. The percentage of abnormal responses in patients with ISHL with vertigo was highest in the cVEMP test, followed by the oVEMP and caloric tests. The vestibular end organs closest to the cochlea tended to be preferentially affected in ISHL with vertigo.
a b s t r a c t Objective: To investigate the extent of vestibular lesions in idiopathic sudden hearing loss (ISHL) with vertigo. Method: We reviewed the clinical records of 25 consecutive new patients with ISHL with vertigo. We classified patients based on their pattern of vestibular dysfunction. All patients showed cochlear damage and were labeled C (cochlear) type. If a patient showed abnormal cervical vestibular evoked myogenic potential (cVEMP), ocular VEMP (oVEMP) or caloric responses, an S (saccule), U (utricule) or L (lateral semicircular canal) respectively was added to their label. Results: All patients underwent cVEMPs and caloric tests. Sixteen (64%) and 13 (52%) showed abnormal cVEMPs and caloric responses, respectively, on the affected side. Among the 23 patients who underwent oVEMPs, 10 (43%) showed abnormal oVEMPs on the affected side. Of these 23 patients, 6 (26%) were classified as C type, 4 (17%) as CS type, 1 (4%) as CL type, 1 (4%) as CSU type, 2 (9%) as CSL type, 1 (4%) as CUL type, 8 (35%) as CSUL type. Conclusion: The vestibular end organs close to the cochlea tended to be preferentially affected. Significance: It is likely that vestibular dysfunction extends from organs close to the cochlea to those further from the cochlea. Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Idiopathic sudden hearing loss (ISHL) is clinically defined as a severe sensorineural hearing loss of sudden onset with unknown
⇑ Corresponding author. Address: Department of Otolaryngology, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan. Tel.: +81 3 5800 8665; fax: +81 3 3814 9486. E-mail address: [email protected] (C. Fujimoto).
cause. Different pathogeneses of sudden hearing loss such as viral infection, vascular obstruction, and cochlear membrane breaks have been proposed (Gussen, 1976; Schuknecht and Donovan, 1986; Schuknecht et al., 1973; Simmons, 1968). Approximately 40% of patients with ISHL also suffer from vestibular symptoms (Nakashima and Yanagita, 1993; Shaia and Sheehy, 1976), which may occur at the onset of hearing loss or be delayed for hours or even days. Vertigo appears more frequently in association with profound hearing loss and the recovery of hearing is worse in patients with vertigo than those without vertigo (Mattox and
http://dx.doi.org/10.1016/j.clinph.2014.07.028 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
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C. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
Simmons, 1977; Nakashima and Yanagita, 1993; Shaia and Sheehy, 1976; Wilson et al., 1982). As for the findings of vestibular function testing in ISHL with vertigo, it has previously been reported that 40% of patients show reduced caloric responses in the affected ear (Iwasaki et al., 2005b; Mattox and Simmons, 1977; Shaia and Sheehy, 1976; Wilson et al., 1982). Caloric testing has been used to clinically assess the lateral semicircular canal and superior vestibular nerve. On the other hand, cervical vestibular evoked myogenic potentials (cVEMPs), recorded from the sternocleidomastoid muscle (SCM) in response to brief pulses of air-conducted sound (ACS), bone-conducted vibration (BCV) or electrical stimulation (Colebatch and Halmagyi, 1992; Halmagyi et al., 1995; Watson et al., 1998), have been used as a clinical test of the saccule and inferior vestibular nerve. Clinical and neurophysiological studies have suggested that cVEMPs to ACS are generated by the activation of saccular afferents (Colebatch et al., 1994; Murofushi and Curthoys, 1997; Murofushi et al., 1995, 1996a,b). Using these vestibular function tests to detect peripheral vestibular dysfunction, our group previously demonstrated that in patients with ISHL with vertigo, the saccule was more frequently involved than the semicircular canals (Iwasaki et al., 2005b). This result was consistent with previous histopathological case studies showing that atrophic changes of the saccular macula were most frequently observed in the vestibular organs of patients with ISHL (Gussen, 1976; Inagaki et al., 2012; Ishii and Toriyama, 1977; Sando et al., 1977; Schuknecht and Donovan, 1986; Yoon et al., 1990). Recently, it has been revealed that short-latency potentials called ocular VEMPs (oVEMPs) can be recorded from beneath the eyes in response to ACS and BCV (Iwasaki et al., 2007; Rosengren et al., 2005). oVEMPs are considered to reflect activity of the inferior oblique muscle and represent vestibular function mediated by a crossed otolith-ocular pathway (Chihara et al., 2007; Iwasaki et al., 2007, 2008; Rosengren et al., 2005; Todd et al., 2007; Weber et al., 2012). oVEMPs mainly reflect the function of the utricle and the superior vestibular nerve (Curthoys et al., 2006, 2011; Iwasaki et al., 2009, 2010). Combined use of cVEMP, oVEMP and caloric tests facilitates a more precise and comprehensive examination of the nervous system. In the present study, we investigated the extent of vestibular lesions in patients with ISHL with vertigo using cVEMP, oVEMP and caloric testing. Furthermore, we evaluated the relationship between the severity of hearing loss and the extent of vestibular dysfunction. 2. Materials and methods 2.1. Study design This retrospective data collection study was approved by the regional ethical standards committee in the Faculty of Medicine at the University of Tokyo and was conducted according to the tenets of the Declaration of Helsinki. 2.2. Subjects We reviewed the clinical records of consecutive new patients with ISHL with vertigo visiting the Balance Disorder Clinic at the University of Tokyo Hospital between January 2008 and December 2012. All of these patients had undergone a detailed history-taking and a battery of tests including a physical examination and standardized neurological, neuro-otological, neuro-ophthalmological and audiological examinations. Eye movements were observed using an infrared charge-coupled device camera and recorded by electronystagmography.
The diagnostic criteria for ISHL with vertigo included a sensorineural hearing loss of more than 30 dB, occurring in at least 3 contiguous frequencies in less than 3 days (Stachler et al., 2012; Wilson et al., 1980), a single attack of vertigo occurring almost simultaneously with the onset of hearing loss, and the absence of other neurological signs. Those patients who had multiple attacks of hearing loss and vertigo were excluded from this study to rule out Mèniére’s disease or migraine. When the cause of SHL and vertigo was unknown, ISHL was considered. In this study, 25 patients with ISHL with vertigo were included [15 men, 10 women, mean (±SD) age 63.6 (±13.6) years, range 20–88]. 2.3. Caloric testing Caloric testing was performed by irrigating the external auditory canal with 2 ml ice water (4 °C) for 20 s followed by aspiration of water. This method of caloric stimulation is easier to perform than bithermal irrigation with water at 30 and 44 °C, and has been shown to have a high sensitivity and specificity for detecting canal paresis (CP) based on Jongkee’s formula (Schmal et al., 2005). Caloric nystagmus was recorded, in a darkened room, using an electronystagmograph. We defined an abnormal caloric response by either of the following criteria: (1) CP percentage >20% (Iwasaki et al., 2005a); (2) maximum slow phase eye velocity 150 lV) were not enrolled in the present study. We were not able to calculate the corrected amplitude for cVEMPs as we did not measure the rectified background activity of the SCMs during the recordings. When no reproducible p13–n23 was present in 2 runs, we regarded it as an ‘‘absent response’’. When a reproducible p13– n23 was present and cVEMP AR (%) was greater than the normal upper limits, we regarded it as a ‘‘decreased response’’. 2.5. oVEMP testing Subjects lay supine on a bed, with their head supported by a pillow and with surface EMG electrodes placed on the skin 1 cm below (active) and 3 cm below (indifferent) the center of each lower eyelid. The ground electrode was placed on the chin. During testing, the subject looked up approximately 30 degrees above
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
C. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
straight ahead and maintained their focus on a small dot approximately 1 m from their eyes. The signals were amplified by a differential amplifier (bandwidth: 0.5–500 Hz), and the unrectified signals were averaged (n = 50) using Neuropack R. The BCV stimuli were 4 ms tone-bursts of 500 Hz vibration (rise/fall time = 1 ms and plateau time = 2 ms) delivered by a hand-held 4810 mini-shaker (Bruel and Kjaer, Naerum, Denmark) fitted with a short rod terminated in a bakelite cap 1.5 cm in diameter, which was placed perpendicularly on the forehead at the hairline, in the midline (Fz). The driving voltage was 80 V peak to peak, and it produced a peak force level of 128 dB re 1 lN. The stimuli were applied 3 times per second, and the time window for analysis was 50 ms. Averages of two sets of 50 stimuli each were computed. Consecutive runs were performed to confirm the reproducibility of the oVEMP responses. We analyzed the first negative peak (nI) latency, the subsequent positive peak (pI) latency, and the amplitude between nI and pI. Amplitude and latency were determined from the average of 2 runs. For the evaluation of amplitude, the asymmetry ratio for nI–pI amplitude (oVEMP AR) was calculated as 100 [(Au Aa)/(Aa + Au)], where Au is the nI–pI amplitude on the unaffected side and Aa is the nI–pI amplitude on the affected side (Chihara et al., 2007). Responses recorded from the eye contralateral to stimulation were used for calculating oVEMP AR. On the basis of the results from normal subjects, the upper limit of normal oVEMP AR was set at 27.3 for oVEMPs to BCV (Iwasaki et al., 2008). When no reproducible nI–pI was present in 2 runs, we regarded it as an ‘‘absent response’’. When a reproducible nI–pI was present and the oVEMP AR (%) was greater than the normal upper limits, we regarded it as a ‘‘decreased response’’.
2.6. Pure tone audiogram Pure tone audiograms were categorized as high- or low-tone hearing loss, flat-type hearing loss, or profound hearing loss. The group with high-tone hearing loss was defined as those patients with an average loss of 4–8 kHz, surpassing the average of 0.25– 0.5 kHz by 30 dB or more. The low-tone hearing loss group demonstrated an average loss of 0.25–0.5 kHz, surpassing the average of 4–8 kHz by 30 dB or more. The flat-type group consisted of patients with a difference between the worst and best hearing levels of 20 dB or less among 6 frequencies: 0.25, 0.5, 1, 2, 4, and 8 kHz. In the group with profound hearing loss, at least 2 frequencies produced results that were off the scale, and the difference between the hearing level and the maximum sound level generated by the audiometer was within 10 dB at all 6 frequencies. The pure tone average (PTA) was calculated with thresholds at 0.5, 1 and 2 kHz.
2.7. Classification of patients We classified patients based on their pattern of vestibular dysfunction. All the patients showed cochlear damage and were labeled C (cochlear) type. If a patient showed abnormal cVEMP, oVEMP or caloric responses, we added an S (saccule), U (utricule) or L (lateral semicircular canal), respectively. For example, if a patient showed abnormal cVEMPs and oVEMPs but normal caloric responses, we classified the patient as a CSU type.
2.8. Statistical analysis The comparison of the PTA between patients with and without an abnormal caloric response was statistically analyzed using the Student’s t-test (p < 0.05). IBM SPSS statistics 21 (IBM Corporation, New York, United States) was used for the statistical analysis.
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3. Results The clinical characteristics of the patients are presented in Table 1. Of the 25 included patients, the right ear was involved in 12 patients (48%), and the left ear was involved in 13 patients (52%). None of the patients showed clear findings of conductive hearing loss; the outer ear and tympanum were assessed, and tympanometry was performed. The audiogram types of the 25 patients were as follows: high-tone hearing loss in 6 (24%), profound hearing loss in 6 (24%), flat-type hearing loss in 13 (52%). There were no patients with low-tone hearing loss. Twenty of the 25 patients (80%) showed spontaneous nystagmus. Among them, 14 patients (70%) showed horizontal nystagmus whereas 6 patients (30%) showed horizontal–torsional nystagmus. Four of the 5 patients (80%) who did not have spontaneous nystagmus had normal responses in both cVEMP and caloric tests. Twenty-three of the 25 patients underwent cVEMP, oVEMP and caloric testing, while the other 2 patients underwent cVEMP and caloric testing, but not oVEMP testing. Among the 25 patients who underwent cVEMP and caloric tests, 16 (64%) showed abnormal cVEMP responses on the affected side and 13 patients (52%) showed abnormal caloric responses on the affected side. Among the 23 patients who underwent oVEMP testing, 10 (43%) showed abnormal oVEMPs on the affected side. The percentage of abnormal responses in patients with ISHL with vertigo was the highest in cVEMP testing. Of the 23 patients who underwent cVEMP, oVEMP and caloric tests, 6 (26%) were classified as C type; 4 (17%) as CS type; 1 (4%) as CL type; 1 (4%) as CSU type; 2 (9%) as CSL type; 1 (4%) as CUL type; 8 (35%) as CSUL type (Fig. 1). No patients were classified as CU type. Table 2 shows the audiometric characteristics in each type of vestibular dysfunction. For investigating the association of the severity of hearing loss with the extent of vestibular dysfunction, a comparison of the PTA between the patients with and without an abnormal caloric response was statistically analyzed. The average PTA was larger in patients with abnormal caloric responses (83.8 dB) than those without abnormal caloric responses (74.3 dB). However, no statistical difference was found (p > 0.05). In patients with profound hearing loss, the percentage of patients with abnormal caloric responses (31%) was larger than those without abnormal caloric responses (17%).
4. Discussion In the present study, we have examined vestibular function in ISHL patients with vertigo using cVEMP, oVEMP and caloric testing. Caloric testing has been used clinically as a test of the lateral semicircular canal and superior vestibular nerve. cVEMPs have been used clinically as a test of the saccule and inferior vestibular nerve (Colebatch et al., 1994; Murofushi et al., 1996b, 1998), although some recent studies have shown involvement of vestibular end organs other than the saccule for generating cVEMPs (Wei et al., 2013; Zhu et al., 2011). oVEMPs have been mainly regarded as a test of the utricle and the superior vestibular nerve (Curthoys et al., 2006, 2011; Iwasaki et al., 2009, 2010), although the origin of the response to ACS remains controversial (Chihara et al., 2007; Curthoys et al., 2011). Using these vestibular function tests, we showed that the percentage of abnormal responses in patients with ISHL with vertigo was highest in the cVEMP test, followed by the oVEMP and caloric tests. Our group has previously demonstrated using cVEMP and caloric testing that the saccule is more frequently damaged than the semicircular canals in patients with ISHL with vertigo (Iwasaki et al., 2005b). Previous histopathological case studies
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
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Table 1 Clinical characteristics of each patient with ISHL with vertigo. Patient no./gender/age
Side
PTA
Type of audiogram
Nystagmus
cVEMP burst
oVEMP BCV
Caloric test
Type of dysfunction
1/M/61 2/M/65 3/F/76 4/M/64 5/F/69 6/M/62 7/M/60 8/F/67 9/F/71 10/F/62 11/M/44 12/M/74 13/M/63 14/M/66 15/M/39 16/F/65 17/M/79 18/M/57 19/M/63 20/F/59 21/F/20 22/M/76 23/M/66 24/F/75 25/F/88
Rt. Lt. Lt. Rt. Lt. Rt. Lt. Lt. Rt. Lt. Lt. Rt. Rt. Lt. Rt. Lt. Lt. Rt. Lt. Lt. Lt. Rt. Lt. Rt. Rt.
26.7 90 66.7 91.7 96.7 105 18.3 83.3 60 115 101.7 60 56.7 63.3 111.7 66.7 45 58.3 73.3 96.7 110 115 115 78.3 76.7
High-tone High-tone Flat-type Flat-type Flat-type Profound High-tone Flat-type Flat-type Profound Flat-type Flat-type High-tone Flat-type Profound High-tone Flat-type Flat-type Flat-type Flat-type Profound Profound Profound Flat type High-tone
No Horizontal–torsional Horizontal No Horizontal No Horizontal Horizontal Horizontal Horizontal Horizontal–torsional Horizontal Horizontal Horizontal Horizontal Horizontal No Horizontal Horizontal Horizontal–torsional Horizontal Horizontal–torsional Horizontal–torsional No Horizontal–torsional
Normal Normal Normal Normal Normal Normal Lt. absence Lt. absence R5d4t. 38.9 Lt. absence Normal Rt. absence Rt. absence Lt. absence Normal Lt. absence Lt. absence Rt. absence Lt. absence Lt. absence Lt. 35.1 Bil. absence Lt. absence Normal Bil. absence
Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Rt. absence Normal Normal Rt. absence Lt. absence Bil. absence Rt. 44.8 Lt. 32.8 Lt. 64.9 Lt. absence Rt. absence Lt. absence N/A N/A
Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Lt. CP 100% Normal Rt. CP33% Lt. CP 36% Rt. CP41% Lt. CP 71% Lt. CP 28% Rt. CP100% Lt. CP 31% Lt. CP 66% Lt. CP 100% Rt. CP68% Lt. CP 64% Normal Rt. CP76%
C C C C C C CS CS CS CS CL CSU CSL CSL CUL CSUL CSUL CSUL CSUL CSUL CSUL CSUL CSUL N/A N/A
ISHL = idiopathic sudden hearing loss, PTA = pure tone average, cVEMP = cervical vestibular evoked myogenic potential, oVEMP = ocular vestibular evoked myogenic potential, BCV = bone-conducted vibration, M = male, F = female, Lt. = left, Rt. = right, N/A = not applicable, CP = canal paresis, AR = asymmetry ratio for p13–n23 or nI–pI amplitude.
Fig. 1. Percentage of C, CS, CU, CL, CSU, CSL, CUL and CSUL types in patients with ISHL with vertigo, and representative data from vestibular tests in a patient of the C, CSU and CSUL types. The C type patient was a 64-year-old male with right ISHL with vertigo who showed normal caloric, cVEMP and oVEMP responses. The CSU type patient was a 74year-old male with right ISHL with vertigo who showed no cVEMP responses on the right side and no oVEMP responses on the left side in the presence of caloric responses. The CSUL type patient was a 44-year-old male with left ISHL with vertigo who showed no cVEMP responses on the left side, abnormal oVEMP responses on the right side and no caloric responses on the left side. cVEMP = cervical vestibular evoked myogenic potential, oVEMP = ocular VEMP, M = male, Rt. = right, Lt. = left, C = cochlear, S = saccule, U = utricle, L = lateral semicircular canal. The black arrowhead shows p13 for cVEMPs or nI for oVEMPs. The white arrowhead shows n23 for cVEMPs or pI for oVEMPs. The horizontal scale bar shows 10 ms for both cVEMPs and oVEMPs. The vertical scale bar shows 100 lV for cVEMPs or 2 lV for oVEMPs.
Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
C. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx Table 2 Audiometric characteristics in each type of vestibular dysfunction in ISHL with vertigo. Type of dysfunction
Number
Median of pure tone average (dB)
Percentage of profound hearing loss (number)
C CS CL CSU CSL CUL CSUL
6 4 1 1 2 1 8
90.9 71.7 101.7 60 60 63.3 85
17% (1) 25% (1) 0% (0) 0% (0) 0% (0) 100% (1) 38% (3)
(26%) (17%) (4%) (4%) (9%) (4%) (35%)
ISHL = idiopathic sudden hearing L = lateral semicircular canal.
loss,
C = cochlear,
S = saccule,
U = utricle,
have reported that atrophy of the saccular macula was most frequently observed in the vestibular organs of patients with ISHL (Gussen, 1976; Inagaki et al., 2012; Ishii and Toriyama, 1977; Sando et al., 1977; Schuknecht and Donovan, 1986; Yoon et al., 1990). The result of the present study is consistent with these previous reports. Patients were classified into C, CS, CSU, CSL or CSUL types; 91% of them belonged to the C, CS, CSU or CSUL type. No patients were classified into the CU, CUL or CL type. These results suggest that the vestibular end organs closest to the cochlea tend to be preferentially affected in ISHL with vertigo. Vestibular dysfunction in ISHL with vertigo may extend from organs close to the cochlea to those further from the cochlea. It has been considered that viral infection is one of the probable causes of ISHL. A previous report indicated that the inner ear pathologies of known viral labyrinthitis cases such as mumps and rubella are similar to that in ISHL (Schuknecht and Donovan, 1986). Microscopic studies of the temporal bones showed that the loss of vestibular hair cells in patients with ISHL was most frequently observed in the saccule but less so in the utricle and semicircular canals, as shown in patients with rubella (Alford, 1968; Lindsay et al., 1953; Schuknecht and Donovan, 1986). Vascular insults have been proposed as another cause of ISHL. In a previous study of the pathophysiology of labyrinthine infarction, the cochlea and the cristae of the anterior and horizontal semicircular canals developed degenerative changes while the utricular macula and the posterior canal ampulla and saccular macula were relatively preserved (Kim et al., 1999). This study proposed that a partial sparing of the inferior vestibular labyrinth may indicate a decreased vulnerability to ischemia because of its better collateral blood supply (Kim et al., 1999). The pattern of the extent of vestibular lesions in our study is similar to the results of vestibular damage in previous temporal bone studies of viral labyrinthitis. Our group have previously reported that the percentage of profound hearing loss was larger in the group which showed abnormal responses in both caloric and cVEMP tests compared with groups which showed normal responses in at least one of these tests (Iwasaki et al., 2005b). In the present study, the average PTA on the affected side and the percentage of profound hearing loss were both larger in patients with abnormal caloric responses than those without abnormal caloric responses. Taken together, it is likely that the more severe the hearing loss is, the more extensive the vestibular lesion might be. However, the number of patients in this study is small and the variance in the PTA in each type seems large. Further investigation using other data sets would be beneficial. This study has several limitations. First, being a retrospective data collection study there is the potential for both selection bias and information bias. Next, the functions of the anterior and posterior semicircular canals were not evaluated in this study. Those patients who were classified into the C type might have also had dysfunction of the anterior and posterior semicircular canals, while
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it is possible that the function of the saccule, the utricle and/or the lateral semicircular canal might have recovered before performing vestibular function tests. In addition, we did not examine any patients with ISHL without vertigo in this study. A previous report described the association between hearing loss and saccular dysfunction in older individuals, although the report did not mention if their patients had symptoms of vestibular dysfunction (Zuniga et al., 2012). We are not sure about whether our findings are specific to the patients exhibiting vertigo. In conclusion, the percentage of abnormal responses in patients with ISHL with vertigo was highest in the cVEMP test, followed by the oVEMP and caloric tests. Most of the patients were classified into C, CS, CSU or CSUL types. These results suggest that the vestibular end organs closest to the cochlea tend to be preferentially affected in ISHL with vertigo. Postural instability in peripheral vestibulopathy associated with abnormal responses in both caloric and cVEMP tests are more severe than when only one of the two tests is abnormal (Fujimoto et al., 2010). Evaluating the extent of vestibular lesions involved in ISHL may be useful for the prognostic prediction of postural stability and help improve the clinical strategy for vestibular rehabilitation practice. Acknowledgement This work was supported by grants from the Ministry of Education, Culture, Sports, Science & Technology in Japan to Chisato Fujimoto. Conflict of interest: None of the authors have potential conflicts of interest to be disclosed. References Alford BR. Rubella-la bete noire de la medecine. Laryngoscope 1968;78:1623–59. Chihara Y, Iwasaki S, Ushio M, Murofushi T. Vestibular-evoked extraocular potentials by air-conducted sound: another clinical test for vestibular function. Clin Neurophysiol 2007;118:2745–51. Colebatch JG, Halmagyi GM. Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 1992;42:1635–6. Colebatch JG, Halmagyi GM, Skuse NF. Myogenic potentials generated by a clickevoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 1994;57:190–7. Curthoys IS, Iwasaki S, Chihara Y, Ushio M, McGarvie LA, Burgess AM. The ocular vestibular-evoked myogenic potential to air-conducted sound; probable superior vestibular nerve origin. Clin Neurophysiol 2011;122:611–6. Curthoys IS, Kim J, McPhedran SK, Camp AJ. Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig. Exp Brain Res 2006;175:256–67. Fujimoto C, Murofushi T, Chihara Y, Suzuki M, Yamasoba T, Iwasaki S. Novel subtype of idiopathic bilateral vestibulopathy: bilateral absence of vestibular evoked myogenic potentials in the presence of normal caloric responses. J Neurol 2009;256:1488–92. Fujimoto C, Murofushi T, Chihara Y, Ushio M, Yamaguchi T, Yamasoba T, Iwasaki S. Effects of unilateral dysfunction of the inferior vestibular nerve system on postural stability. Clin Neurophysiol 2010;121:1279–84. Gussen R. Sudden deafness of vascular origin: a human temporal bone study. Ann Otol Rhinol Laryngol 1976;85:94–100. Halmagyi GM, Yavor RA, Colebatch JG. Tapping the head activates the vestibular system: a new use for the clinical reflex hammer. Neurology 1995;45:1927–9. Inagaki T, Cureoglu S, Morita N, Terao K, Sato T, Suzuki M, et al. Vestibular system changes in sudden deafness with and without vertigo: a human temporal bone study. Otol Neurotol 2012;33:1151–5. Ishii T, Toriyama M. Sudden deafness with severe loss of cochlear neurons. Ann Otol Rhinol Laryngol 1977;86:541–7. Iwasaki S, Chihara Y, Smulders YE, Burgess AM, Halmagyi GM, Curthoys IS, et al. The role of the superior vestibular nerve in generating ocular vestibular-evoked myogenic potentials to bone conducted vibration at Fz. Clin Neurophysiol 2009;120:588–93. Iwasaki S, McGarvie LA, Halmagyi GM, Burgess AM, Kim J, Colebatch JG, et al. Head taps evoke a crossed vestibulo-ocular reflex. Neurology 2007;68:1227–9. Iwasaki S, Murofushi T, Chihara Y, Ushio M, Suzuki M, Curthoys IS, et al. Ocular vestibular evoked myogenic potentials to bone-conducted vibration in vestibular schwannomas. Otol Neurotol 2010;31:147–52. Iwasaki S, Smulders YE, Burgess AM, McGarvie LA, Macdougall HG, Halmagyi GM, et al. Ocular vestibular evoked myogenic potentials in response to boneconducted vibration of the midline forehead at Fz. A new indicator of unilateral otolithic loss. Audiol Neurootol 2008;13:396–404.
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Please cite this article in press as: Fujimoto C et al. Involvement of vestibular organs in idiopathic sudden hearing loss with vertigo: An analysis using oVEMP and cVEMP testing. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.07.028
