Original Paper Audiology Neurotology

Received: October 18, 2014 Accepted after revision: January 20, 2015 Published online: May 9, 2015

Audiol Neurotol 2015;20:229–236 DOI: 10.1159/000375395

Diagnostic Value of Frequency-Associated Vestibular-Evoked Myogenic Potential Responses in Ménière’s Disease Mehti Salviz a Turgut Yuce a Abdullah Karatas a Hasan Huseyin Balikci b Murat Haluk Ozkul a   

 

 

 

 

Department of ORL, Haseki Training and Research Hospital, Istanbul, and b Department of ORL, Susehri Government Hospital, Sivas, Turkey  

 

Key Words Ménière’s disease · Vestibular-evoked myogenic potential · Inner ear · Saccule · Utricle

Abstract Thirty subjects with unilateral Ménière’s disease (MD) and 18 age-matched controls underwent cervical (cVEMP) and ocular vestibular-evoked myogenic potential (oVEMP) testing using bilateral air-conducted stimulation (ACS) with stimulus frequencies of 500 and 1,000 Hz. The aim of this study is to determine the diagnostic value of frequency-associated responses in MD using oVEMP and cVEMP following 500and 1,000-Hz ACS. In healthy controls and unaffected ears, responses to 500 Hz were found better than 1,000-Hz ACS in both oVEMP and cVEMP, while ears with MD responded to 1,000-Hz ACS better than to 500-Hz ACS in oVEMP. In cVEMP tests, affected ears responded to 500-Hz and 1,000-Hz ACS equally. Amplitude ratios of 1,000/500 Hz in both oVEMP and cVEMP were successful in differing affected ears from unaffected ears and healthy controls. This study showed frequency alteration of oVEMP and cVEMP can be used as a diagnostic test battery in MD. © 2015 S. Karger AG, Basel

© 2015 S. Karger AG, Basel 1420–3030/15/0204–0229$39.50/0 E-Mail [email protected] www.karger.com/aud

Introduction

Ménière’s disease (MD) is characterized by hydrops of the endolymphatic space, vertigo, tinnitus, aural fullness and hearing loss. Since Ménière first described MD in 1861, its pathogenesis has remained unclear. Although several tests are reported for the diagnosis, there is currently no gold standard test, with MD typically being diagnosed clinically using the criteria of the American Academy of Otolaryngology, Head and Neck Surgery (AAOHNS) published in 1995. However, where the diagnosis remains uncertain, no validated diagnostic tool exists. Vestibular-evoked myogenic potentials (VEMP) are generated by the utricle and saccule in response to acoustic and vibratory stimulation [Colebatch and Halmagyi, 1992; Todd et al., 2000]. Cervical VEMP (cVEMP) are short latency (approximately 13 ms) inhibitory potentials recorded from sternocleidomastoid muscles following saccular stimulation by air-conducted sound (ACS) or bone-conducted vibration. Ocular VEMP (oVEMP) are excitatory potentials of approximately 10 ms, recorded from contralateral extraocular muscles in response to bone-conducted vibration or ACS stimulation of the utricle [Rosengren et al., 2005; Todd et al., 2007] and provide complementary data to cVEMPs. VEMPs stimulated by Mehti Salviz, MD Haseki Egitim ve Arastirma Hastanesi Kulak Burun Bogaz Klinigi TR–34096 Istanbul (Turkey) E-Mail salvizm @ yahoo.com

Downloaded by: NYU Medical Center Library 128.122.253.228 - 5/20/2015 7:32:30 PM

a

Material and Methods Subjects Thirty patients diagnosed with definite MD according to AAOHNS criteria were enrolled. The age range was 24–75 years (mean 44.5 ± 10.5 years). All subjects had unilateral disease, and none had sensorineural hearing loss or aural fullness affecting the contralateral ear. A vestibular test battery comprising bithermal caloric stimulation, and cVEMP and oVEMP testing was employed in all patients. Magnetic resonance imaging evaluation was also undertaken in all subjects to exclude retrolabyrinthine pathology. Audiometric evaluation was performed at frequencies of 500, 1,000, 2,000 and 3,000 Hz, and patients were grouped according to AAOHNS guidelines: stage I, 0–25 dB hearing level (HL); stage II, 25–40

230

Audiol Neurotol 2015;20:229–236 DOI: 10.1159/000375395

Table 1. Descriptive characteristics of study population (n = 30)

Male/female Age, years Disease duration, months Pure tone average (0.5–3 kHz), dB Canal paresis, % Stage, n I II III IV

12/18 44.5±10.5 (range 24–75) 50.8±50.2 (range 9–207) 44.2±24.6 (range 18–78) 35.9±20.8 (range 9–75) 4 7 17 2

Values are expressed as means ± SD.

dB HL; stage III, 41–70 dB HL, and stage IV worse than 70 dB HL. The descriptive characteristics of the study population are shown in table 1. Eighteen age-matched volunteers, aged between 22 and 67 years (mean 44.9 ± 11.0 years) were enrolled in the control group. The mean age did not statistically significantly differ between the control group and MD subjects (p = 0.851). Control subjects had no vestibular or hearing problems, and no history of ear disorders either. All of them had normal hearing levels assessed by pure tone audiogram and tympanograms. All control subjects underwent cVEMP and oVEMP testing bilaterally (18 subjects, 36 ears). The study was approved by our institution’s ethics committee (protocol No. 67/2014), and written informed consent was obtained from all individuals before the recordings. Stimulus Design and Recording Setup Both oVEMP and cVEMP were generated in MD patients using bilateral air conduction tone bursts with stimulus frequencies of 500 and 1,000 Hz to test both the affected and unaffected ears. All recordings were performed with the disease in its quiescent state, with no patients suffering vertiginous attacks at the time of assessment. The stimuli were presented monaurally, using a pair of calibrated ABR3A insert earphones at a maximum intensity of 100 dB nHL. The stimulus profile was set to produce a 2-ms rise, 2-ms plateau and 2-ms fall time with a 5.1-Hz repetition rate. Frequencies were presented 50– 150 times in order to average responses. In order to minimize fatigue, at least 30 s of resting time was set between each run. VEMP recordings were performed using an Eclipse EP 25 VEMP evoked potential system (Interacoustics AS, Assens, Denmark). Disposable silver/silver chloride electrodes were used for recordings. The ground electrodes were placed on the forehead, and the impedance of each electrode was ≤3 kΩ. An EMG feedback system (Interacoustics Eclipse, Assens, Denmark) was used for recordings enabling participants to maintain muscle tone between 50 and 200 μV. The EMG was amplified (60 dB), bandpass filtered (10–750 Hz) and recorded from 10 ms before stimulus onset to 60 ms afterward. In order to reduce interpatient variability, the test was performed at least twice to ensure reproducibility, and cVEMP responses were normalized by dividing raw amplitudes by background EMG activity. Results were categorized into 3 groups: affected ear, unaffected ear and control group. Data were collected

Salviz/Yuce/Karatas/Balikci/Ozkul

Downloaded by: NYU Medical Center Library 128.122.253.228 - 5/20/2015 7:32:30 PM

ACS rely on sound transmission to the otolithic organs through the middle ear, oval window and vestibule, and require the structural integrity of the middle ear conducting system, otolithic organs, and the saccule and utricle. VEMP are a useful diagnostic tool in superior canal dehiscence and have also been used to diagnose MD. Patients with MD have been shown to have lower VEMP than normal controls [Winters et al., 2012], though it has also been demonstrated that VEMP can be normal or even augmented, particularly in the earlier stages of the disease [Wen et al., 2012; Young et al., 2003]. Although several studies showed subjects with MD to have significant abnormalities in cVEMP and oVEMP, there is wide variation in the results [Taylor et al., 2011]. Rauch et al. [2004] first reported that the optimal frequency of ACS of cVEMP in MD was increased to 1,000 Hz, in contrast to 500 Hz in normal ears. This finding is supported by other studies [Kim-Lee et al., 2009; Sandhu et al., 2012], and amplitude ratios of cVEMP stimulated by 1,000/500 Hz have been proposed as a diagnostic marker for MD with high sensitivity and specificity. Similar frequency shifting is also described in oVEMP results for patients with MD [Sandhu et al., 2012; Winters et al., 2012]. On the other hand, VEMP amplitudes, thresholds and frequency dynamics are known to be affected by age [Piker et al., 2011, 2013], with older subjects showing a shift to higher frequencies (750 or 1,000 Hz rather than 500 Hz) and lower amplitudes of best ACS, compared to younger subjects. There is a strong argument for using age-adjusted controls in frequency-tuning studies for MD, and additional studies are needed to assess the frequency dynamics of both oVEMP and cVEMP using age-matched controls. We aimed to determine the diagnostic value of frequency-associated responses of oVEMP and cVEMP in MD using 500- and 1,000-Hz ACS, and the cutoff value to discriminate MD from healthy controls.

2 μV

Normal subject

MD patient

N1

N1 500 Hz

P1

N1 N1

PA 1,000 Hz P1 P1

0

10

20

30 40 Time (ms)

50

60

0

10

20

30 40 Time (ms)

50

60

Fig. 1. Example of the oVEMP waveform recorded from a healthy subject and patient with MD in response to

500- and 1,000-Hz tone bursts.

determined by the Wilcoxon signed-rank test; between-group differences (MD vs. controls) were assessed using the Mann-Whitney U test. Student’s t test was used for normally distributed variables (e.g. subject ages within the groups). Correlations between VEMP responses and age were determined by using the Spearman test. The capacity of the VEMP test to predict the presence of MD was analyzed using a ROC (receiver-operating characteristics) curve. When a significant cutoff value was observed, sensitivity and specificity were presented. Statistical significances were accepted as p < 0.05 and 0.05).

1,000/500-Hz amplitude ratio

1.50

1.40

1.25

1.20

1.00

1.00

0.80

0.75

0.60 0.50 0.40 0.25 20.00

a

30.00

40.00

50.00

60.00

70.00

Age (years)

20.00

30.00

40.00

b

50.00

60.00

70.00

Age (years)

In earlier reports, the optimal stimulation frequency in healthy subjects is reported to be 500 Hz for cVEMP and with reduced amplitudes for 1,000 versus 500 Hz [Murofushi et al., 2009; Rauch et al., 2004; Welgampola and Colebatch, 2001]. Similar findings are also reported for oVEMP responses in healthy subjects [Chihara et al., 2009; Murnane et al., 2011]. However, it is reported that 500 Hz is not always the best stimulation frequency; for some subjects, 750 or 1,000 Hz might be optimal [Piker et al., 2013; Taylor et al., 2012]. The effect of stimulus frequency on the amplitude of cVEMP responses varies with age, with young adults giving peak amplitudes at 750 Hz, while older adults required 1,000-Hz stimulation [Piker et al., 2013]. Piker et al. [2011] also reported that amplitudes tend to decrease with age, and this effect is particularly pronounced in subjects older than 50 years. These reports demonstrate the importance of age adjustment in frequency-tuning investigations involving cVEMP and oVEMP. In this regard, it is very important to test the diagnostic value of both oVEMP and cVEMP in MD using age-matched controls. Therefore, we analyzed the relationship between age and VEMP responses to determine whether the age is an influential factor in our study group or not. We observed that 1,000/500-Hz amplitude ratios in both oVEMP and cVEMP increased as age increased in healthy controls. There was a similar relationship be-

tween age and amplitude ratio in subjects with MD as well, but it was not statistically significant. Actually, our study does not have a large enough age-stratified population and is not designed to make such a comparison. Nevertheless, our findings support the importance of setting an age-matched control group. The alteration of frequency characteristics in MD can be explained by the mass stiffness theory proposed by Todd et al. [2000]. The mass of the otoconia of the otolith organs limits high frequency responses whereas stiffness of the membranous labyrinth limits low frequency ones. Distension in the otolith organs can change this biomechanical concept with an increased stiffness of the membranous labyrinth. Endolymphatic hydrops can cause increased stiffness of otolith organs, particularly in the saccule. However, an increased amplitude ratio is more prominent in oVEMP than cVEMP despite the fact that utricular hydrops is less common than saccular hydrops [Merchant et al., 2005]. Sandhu et al. [2012] also showed a similar dissociation between cVEMP and oVEMP in MD. According to their findings, the optimal frequency observed in oVEMP was higher than cVEMP, 1,000 versus 750 Hz. Those results suggested there might be additional factors that have influence on the alteration of frequency-dependent responses. Those reasons might be the reduction of otolith organ mass or loss of hair cells [Tay-

Frequency-Associated VEMP Responses in Ménière’s Disease

Audiol Neurotol 2015;20:229–236 DOI: 10.1159/000375395

235

Downloaded by: NYU Medical Center Library 128.122.253.228 - 5/20/2015 7:32:30 PM

Fig. 8. Scatterplots illustrating a positive relationship between age and 1,000/500-Hz amplitude ratios of cVEMP (a) and oVEMP (b) in healthy controls (r2 = 0.149 for cVEMP and r2 = 0.219 for oVEMP).

lor et al., 2012], particularly when considering that VEMP responses seem to shift up to high frequencies as age increases. Mechanical properties are likely to be the principal factor underlying frequency tuning, though other factors such as electrical resonance of the hair cell ionic currents or central projections may have a role. In this study, the VEMP response rate was slightly higher than that of previous studies, particularly for oVEMP recordings in subjects with MD. This can be attributed to the lower age of our study population. On the other hand, there was a considerable amount of missing data, which was filled by using a regression imputation method. The results about cVEMP did not change significantly after imputation. However, the amplitude ratio for oVEMP has changed from an insignificant to significant difference between affected and unaffected ears after imputation. VEMP response rates were very similar in affected and unaffected ears. Therefore, the need for imputation was similar for affected and unaffected ears. By this method, we were able to take all VEMP recordings into account and this has increased the power of our study. Jerin et al. [2014] defined amplitudes as 1 μV in their study if they were not able to get any VEMP re-

sponse. This method was not suitable for our study, hence dividing our oVEMP responses by 1 would have given a very high amplitude ratio in several subjects and could have significantly influenced the results. In conclusion, we investigated the diagnostic value of frequency-associated VEMP responses in MD using agematched controls. This study showed that frequency-dependent responses in MD were deviated from 500 to 1,000 Hz in comparison to healthy controls. The amplitude ratios of 1,000/500 Hz in both oVEMP and cVEMP in MD are successful in differing ears with MD from healthy subjects. These results suggest VEMPs may be a useful diagnostic tool particularly in early MD or where there is diagnostic uncertainty. However, it seems using an age-matched control group has slightly decreased the diagnostic value of cVEMP in MD compared to previous reports, and additional studies using age-matched controls are needed in this regard. Conflict of Interest The authors report no financial relationship with any organization and no conflicts of interest.

Chihara Y, Iwasaki S, Fujimoto C, Ushio M, Yamasoba T, Murofushi T: Frequency tuning properties of ocular vestibular evoked myogenic potentials. Neuroreport 2009; 28: 1491– 1495. Colebatch JG, Halmagyi GM: Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 1992;42:1635–1636. Jerin C, Berman A, Krause E, Ertl-Wagner B, Gürkov R: Ocular vestibular evoked myogenic potential frequency tuning in certain Ménière’s disease. Hear Res 2014;310:54–59. Kim-Lee Y, Ahn JH, Kim YK, Yoon TH: Tone burst vestibular evoked myogenic potentials: diagnostic criteria in patients with Ménière’s disease. Acta Otolaryngol 2009;129:924–928. Merchant SN, Adams JC, Nadol JB Jr: Pathophysiology of Ménière’s syndrome: are symptoms caused by endolymphatic hydrops? Otol Neurotol 2005;26:74–81. Murnane OD, Akin FW, Kelly KJ, Byrd S: Effects of stimulus and recording parameters on the air conduction ocular vestibular evoked myogenic potential. J Am Acad Audiol 2011; 22: 469–480. Murofushi T, Ozeki H, Inoue A, Sakata A: Does migraine-associated vertigo share a common pathophysiology with Ménière’s disease? Study with vestibular-evoked myogenic potential. Cephalalgia 2009;29:1259–1266.

236

Node M, Seo T, Miyamoto A, Adachi A, Hashimoto M, Sakagami M: Frequency dynamics shift of vestibular evoked myogenic potentials in patients with endolymphatic hydrops. Otol Neurotol 2005;26:1208–1213. Piker EG, Jacobson GP, Burkard RF, McCaslin DL, Hood LJ: Effects of age on the tuning of the cVEMP and oVEMP. Ear Hear 2013;34:65–73. Piker EG, Jacobson GP, McCaslin DL, Hood LJ: Normal characteristics of the ocular vestibular evoked myogenic potential. J Am Acad Audiol 2011;22:222–230. Rauch SD, Zhou G, Kujawa SG, Guinan JJ, Herrmann BS: Vestibular evoked myogenic potentials show altered tuning in patients with Ménière’s disease. Otol Neurotol 2004;25:333–338. Rosengren SM, McAngus Todd NP, Colebatch JG: Vestibular-evoked extraocular potentials produced by stimulation with bone-conducted sound. Clin Neurophysiol 2005;116:1938– 1948. Sandhu JS, Low R, Rea PA, Saunders NC: Altered frequency dynamics of cervical and ocular vestibular evoked myogenic potentials in patients with Ménière’s disease. Otol Neurotol 2012;33:444–449. Taylor RL, Bradshaw AP, Halmagyi GM, Welgampola MS: Tuning characteristics of ocular and cervical vestibular evoked myogenic potentials in intact and dehiscent ears. Audiol Neurootol 2012;17:207–218.

Audiol Neurotol 2015;20:229–236 DOI: 10.1159/000375395

Taylor RL, Wijewardene AA, Gibson WP, Black DA, Halmagyi GM, Welgampola MS: The vestibular evoked-potential profile of Ménière’s disease. Clin Neurophysiol 2011;122:1256–1263. Todd NP, Cody FW, Banks JR: A saccular origin of frequency tuning in myogenic vestibular evoked potentials? Implications for human responses to loud sounds. Hear Res 2000;141:180–188. Todd NP, Rosengren SM, Aw ST, Colebatch JG: Ocular vestibular evoked myogenic potentials (OVEMPs) produced by air- and bone-conducted sound. Clinical Neurophysiol 2007;118: 381–390. Welgampola MS, Colebatch JG: Characteristics of tone burst-evoked myogenic potentials in the sternocleidomastoid muscles. Otol Neurotol 2001;22:796–802. Wen MH, Cheng PW, Young YH: Augmentation of ocular vestibular-evoked myogenic potentials via bone-conducted vibration stimuli in Ménière disease. Otolaryngol Head Neck Surg 2012;146:797–803. Winters SM, Berg IT, Grolman W, Klis SF: Ocular vestibular evoked myogenic potentials: frequency tuning to air-conducted acoustic stimuli in healthy subjects and Ménière’s disease. Audiol Neurootol 2012;17:12–19. Young YH, Huang TW, Cheng PW: Assessing the stage of Ménière’s disease using vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 2003;129:815–818.

Salviz/Yuce/Karatas/Balikci/Ozkul

Downloaded by: NYU Medical Center Library 128.122.253.228 - 5/20/2015 7:32:30 PM

References

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

Thirty subjects with unilateral Ménière's disease (MD) and 18 age-matched controls underwent cervical (cVEMP) and ocular vestibular-evoked myogenic po...
244KB Sizes 0 Downloads 8 Views