Research in Vestibular Science Vol. 17, No. 2, June 2018 Original Article pissn 2092-8882, eissn 2093-5501 https://doi.org/10.21790/rvs.2018.17.2.44 메니에르병에서경부 Vestibular Evoked Myogenic Potential 과반응의양상 : 예비연구 윤소연, 김미주, 김민범 가톨릭관동대학교국제성모병원이비인후과학교실 Hyper-response of Cervical Vestibular Evoked Myogenic Potential in Patients with Meniere Disease: A Preliminary Study Soyeon Yoon, Mi Joo Kim, Minbum Kim Department of Otorhinolaryngology-Head and Neck Surgery, Catholic Kwandong University, International St. Mary s Hospital, Incheon, Korea Received May 6, 2018 Revised Jun 4, 2018 Accepted Jun 5, 2018 Corresponding Author: Minbum Kim Department of Otorhinolaryngology-Head and Neck Surgery, Catholic Kwandong University, International St. Mary s Hospital, 25, 100 Gil Simgok-ro, Seo-gu, Incheon 22711, Korea Tel: +82-32-290-3052 Fax: +82-32-290-3050 E-mail: minbumkim78@gmail.com ORCID code: https://orcid.org/0000-0002-8051-1403 Copyright c 2018 by The Korean Balance Society. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives: The purpose of this study is to investigate the hyper-responsiveness of cervical vestibular-evoked myogenic potential (cvemp) in patients with Meniere disease (MD), and to compare the result of cvemp between probable and definite MD group. Methods: A total of 110 patients satisfied with probable MD and definite MD criteria, which is recently formulated by the Classification Committee of the Bárány Society, were included. An interpeak amplitude and interaural amplitude difference (IAD) ratio of both ears was measured. The abnormal response of ipsi-lesional cvemp was categorized into 2 groups; hyper-response and hypo-response. Chi-square test and Mann-Whitney U-test were used for statistical analysis. Results: In the probable MD and definite MD group, the mean IAD was 25.24%±17.79% and 53.82%±34.98%, respectively (p<0.01). The abnormal response of cvemp at the affected ear was more frequent in the definite MD group, compared to the probable MD group (32/40 vs. 13/36, p<0.01). However, hyper-response was more frequently observed in the patients with probable MD, compared to the patients with definite MD (13/36 vs. 3/40, p<0.01). Conclusion: Hyper-response of cvemp was more frequently observed in the early probable MD patients. It might be an early sign of MD, related with the saccular hydrops, which can help the early detection and treatment. Res Vestib Sci 2018;17(2):44-48 Keywords: Meniere disease; Vestibular-evoked myogenic potential; Saccular hydrops 서론전정유발근전위 (vestibular evoked myogenic potential, VEMP) 는 Colebatch와 Halmagyi [1] 가처음소개한이후, 점 차임상적으로중요한전정검사로인정받아현재널리사용되고있다. 이중경부전정유발근전위 (cervical VEMP, cvemp) 는청각자극이후경부근육에서유발되는억제성근전위반응으로, 이석기관 (otolith organ) 중특히구형낭 44
윤소연외 2 인. 메니에르병에서경부 VEMP 과반응의양상 (saccule) 의기능을평가할수있다는것이다른전정기능검사와차별되는점이다 [2]. 여러전정질환에서 cvemp 이상이발견되는데, 이는병측 cvemp의반응강도에따라크게두종류로나눌수있다. 첫째는병측에서 cvemp 반응강도가감소되는형태로, 전정신경염또는전정편두통일부에서관찰된다 [3]. 이와반대로병측에서반응강도가증대 (augmentation) 되어과반응 (hyper-response) 을보이는경우도있는데, 이는상반고리관피열증후군 (superior canal dehiscence syndrome, SCDS) 에서흔히관찰되는형태이다 [4]. 메니에르병환자에서도 cvemp 이상소견이흔하게관찰되는데, 특히급성발작시 67% 에서 cvemp 이상이발견된다고보고된바있다 [5]. 흥미롭게도메니에르병에서는병측의 cvemp 반응이상기기술한두가지형태모두로나타날수있다. 특히, Young 등 [6] 은 30% 의메니에르병환자에서 SCDS에서처럼병측 cvemp 반응강도가건측보다큰 cvemp의과반응이관찰된다고보고하였다. 이런 cvemp 과반응은메니에르병초기상태에서자주관찰되는것으로알려져있는데, 구형낭의내림프수종으로인해큰소리에대한구형낭막의반응이민감해져서발생할것으로추정된다 [7]. 이연구에서는 (1) 메니에르병에서 cvemp 과반응의양상에대해조사하고, (2) 새로운진단기준에따른메니에르병아형 (probable vs. definite) 별 cvemp 반응의차이에대해연구해보고자한다. 대상및방법 폰을통해음자극을주고, 이에의해유발된전위를측정하였다. 자극음은 500 Hz의 Tone burst 음으로크기는 90 db nhl이었으며, 각귀에서 120회반복자극을시행하였다. cvemp 강도 ( V) 는 p13 피크와 n23 피크간차이를측정하였고, 양측귀사이차이인이간차 interaural difference (IAD) 값은 ( 우측강도-좌측강도 )/( 우측강도+좌측강도 ) 100 값의절대치 (%) 로정의하였다. 본원검사실서시행한정상대조군 (n=30, 20 60세 ) 에서얻은평균값 (12.40%±6.84%) 을참고하여 IAD 값이 26.09% (mean+2 standard deviation) 이하인경우정상범위로간주하였다. 비정상을보인경우중, (1) IAD가 26.09% 이상이며, 병측에서의 cvemp 강도가더큰경우 과반응 으로, (2) IAD가 26.09% 이상이며, 병측에서의 cvemp 강도가더작은경우를 저반응 으로정의하였다. Probable 메니에르병환자군과 definite 메니에르병환자군의결과를비교하기위해 Mann-Whitney U 검정및카이제곱검정을사용하였고, p 값이 0.05 미만인경우통계적으로유의한것으로판정하였다. 결과최종분석한환자 76명의나이는 24에서 74세였고, 중간값은 52세였다. 남자 12명, 여자 64명으로여자가많았으며, 새로운진단기준상 probable 메니에르병에해당하는경우는 36명, definite 메니에르병에해당하는경우가 40명이었다. 2017년 1월 1일부터 2017년 12월 31일까지 1년간대학병원이비인후과에내원한외래또는입원환자중새로운메니에르병진단기준 (2015 Barany society) [8] 에부합하는 probable 및 definite 메니에르병환자 110명의진료기록을후향적으로분석하였다. 이중 (1) 순음청력검사상기도-골도차가 15 db 이상으로측정되는전도성난청이있는경우, (2) 만성중이염, 양성돌발성체위현훈및전정편두통등의기타질환으로인한현훈을배제할수없는경우및 (3) 외래추적도중소실된경우 34명을제외하고, 최종적으로총 76명의진료기록및전정기능검사결과를분석하였다. 사용된 cvemp의측정방법은다음과같다. 이중차폐가가능한방음실에서피검자를편하게앉아있게한이후, 흉쇄유돌근 (sternocleido mastoid muscle) 에표면전극을부착하였다. 고개를검사반대측으로최대한돌린상태에서이어 Fig. 1. The result of interaural difference (IAD) of all patients. The IAD score of definite Meniere disease (MD) group was marked as blue-diamond dots, and probable MD group as red-rectangular dots. 45
1. Probable 메니에르병환자군 (n=36) 모든환자에서병측 cvemp 반응이관찰되었으며, 평균 IAD 값은 25.24%±17.79% 였다 ( 적색사각형, Fig. 1). cvemp 강도가비정상을보이는경우는 13명 (36.1%) 이었으며, 이중 13명모두에서과반응을보였으며, 저반응을보이는경우는관찰되지않았다. 2. Definite 메니에르병환자군 (n=40) 총 40명중 10명의환자에서병측 cvemp 반응이관찰되지않았으며, 평균 IAD 값은 53.82%±34.98% 로 ( 청색마름모꼴, Fig. 1), 이는 probable 메니에르병환자군에비해높았다 (Table 1) (p<0.01). cvemp 강도가비정상을보이는경우는 32명 (80.0%) 으로 probable 메니에르병환자군에비해흔하게관찰되었다 (Table 1) (p<0.01). 하지만, 40명의 definite 메니에르병환자중 3명 (7.5%) 에서만과반응을보였고, 나머지 29명 (72.5%) 에서는저반응을보였다. 3. 두군의 cvemp 과반응양상 가이상소견을보이는데 [6], 유발전위반응이없거나, 강도가감소또는증가하거나 [7], 가장큰반응이관찰되는음자극주파수변동 (shift of the best frequency) 이확인되었다 [9]. 또한최근 Okumura 등 [10] 에의하면, MR 영상으로전정내림프수종이확인된환자의 71% 에서 cvemp 이상이관찰되었으며, 병이진행함에따라 cvemp 무반응을보이는환자수가현저하게증가하였다 [11]. 게다가메니에르병에서저음역난청이있는경우에서단순돌발성난청과달리유의한 cvemp 이상을보였다 [12]. 따라서 cvemp가메니에르병진단과현재질병단계를파악하는데도움이될수있을것으로기대된다. 하지만, 여전히 cvemp의가치가제한적이라는주장도있다. Johnson 등 [13] 은메니에르환자군에서병측및환측 cvemp 강도에차이가없었다고보고하고있고, 양측 cvemp 이간차가정상군에서의값과중첩되는부분이있어진단적가치가낮다는보고도있었다 [14]. 또한메니에르병진단에있어, cvemp의민감도및특이도가각각 50.0% 와 48.9% 로낮았기때문에, 단일검사로서의가치는제한적이라는주장도있었다 [15]. 이렇게메니에르병환측의 cvemp 결과가일정하지않 Probable 메니에르병환자군에서는 36명중 13명 (36.1%) 에서상대적으로흔하게과반응을보였으나, definite 메니에르병환자군에서는 40명중 3명 (7.5%) 에서만관찰되었다 (Fig. 2) (p<0.01). 각군에서과반응을보인경우, 환자들의 IAD 값은각군에서 43.05%±10.95%, 53.03%±24.18% 였다. 고 찰 경부 VEMP는이론적으로구형낭의기능을반영하기때문에메니에르병진단에도움이될것으로생각되지만, 아직실제임상적가치에대해서는논란이있다. 메니에르병급성발작시많은환자에서병측에서 cvemp Fig. 2. The proportion of patients with hyper-response of cervical vestibular-evoked myogenic potential. MD, Meniere disease. Table 1. The comparison between definite Meniere s disease (MD) and probable MD groups Variable Probable MD group (n=36) Definite MD group (n=40) p-value IAD of amplitude (%) 25.24±17.79 53.82±34.98 <0.01* Ratio of abnormal IAD 13/36 (36.1) 32/40 (80.0) <0.01* Values are presented as mean±standard deviation or number (%). The mean interaural difference (IAD) was higher in the definite MD group, and the abnormal response of cervical vestibular-evoked myogenic potential at the affected ear was more frequent in the definite MD group. *p<0.01. 46
윤소연외 2 인. 메니에르병에서경부 VEMP 과반응의양상 게나오는이유중하나는, 메니에르병환자군의불균질성 (heterogeneity) 때문으로생각한다. 메니에르병은넓은스펙트럼을가진질환으로, 질병초기및후기, probable군및 definite군등시기와질병상태에따라다양한임상양상을보일수있기때문에, VEMP 결과도다양하게나올수있겠다. 실제로 cvemp 결과는같은환자에서도병의상태에따라변할수있는데, 급성발작후 48시간이후에 50% 의환자에서 cvemp가정상으로회복되었다는보고가있을뿐만아니라 [16], 질병초기에 glycerol 또는 furosemide를주입하였을때 cvemp가변화되기도하였다 [17,18]. 메니에르병에서관찰되는 cvemp 과반응은주로질병초기에발생하는것으로생각되는데, 이는구형낭성내림프수종이심해지면구형낭막이등골 (stapes) 에가까워지거나붙게되어, 큰음자극에민감해지기때문일것으로추정된다 [6]. 동물실험에서내림프낭절제이후구형낭내림프수종이수일내로발생하는데, 이는와우및난형낭보다앞서발생하는것으로알려져있다 [19]. 또한바소프레신유도급성발작모델에서도바소프레신주입직후한시간이내에심한구형낭의내림프수종이관찰되었다 [20]. 이연구결과에서, 대다수의 cvemp 과반응은 probable 메니에르병에서발생하였다. 이는와우의심한내림프수종이발생하기전에구형낭내림프수종이발생하였기때문으로추정된다. 즉, 와우병변으로발생하는난청이전에, 구형낭병변으로인한현훈이먼저반복적으로발생하여 probable 메니에르병으로진단된것이다. 이단계에서 cvemp 대부분이정상범위에있었던것도이런구형낭의병변이가역적, 일시적으로일어났기때문으로해석할수있겠다. 반대로, 대부분의 definite 메니에르병에서는주로 cvemp 저반응을보였는데, 이는질병이진행함에따라구형낭뿐만아니라와우까지전반적인내림프수종이심해져청력및 cvemp의비가역적변화가일어난것으로해석할수있겠다. 만약이가설이합당하다면, cvemp 과반응이메니에르병조기진단및감별진단에있어중요한지표가될수있겠다. 예를들면, cvemp 과반응을보이는재발성현훈환자의경우, 메니에르병의초기상태 ( 초기구형낭내림프수종 ) 일가능성을고려하여, 저염식및카페인같은유발물질회피등의생활습관교정을시작하는것도가능하겠다. 하지만, 이가설을명확히검증하기위해서는, 향후연속적인 cvemp 검사를통해질병의상태에따라 cvemp 강도가어떻게변화하는지에대한전향적연구가선행되어야 할것으로생각한다. 또한, probable 메니에르병의진단기준이다소광범위하기때문에, 이연구에서포함된환자군중일부가추후전정편두통등의질환으로진단될수있을가능성이있다. 따라서, 장기간의추적과연속적인검사를통해 probable 메니에르병환자군일부가다른질환으로진단되지않는지, 또는 definite 메니에르병환자로전환되는지확인하는것이필요하겠다. 결 새로운진단기준에따른 probable 메니에르병에서 cvemp 과반응이 definite 메니에르병에서보다흔하게관찰되었다. cvemp 과반응은구형낭내림프수종과관련한메니에르병의초기지표일가능성이있으며, 향후메니에르병의조기진단과치료에도움을줄수있을것으로기대한다. 론 중심단어 : 메니에르병, 전정근유발전위, 구형낭수종 이해관계 (CONFLICT OF INTEREST) 저자들은이논문과관련하여이해관계의충돌이없음을명시합니다. 감사의글 (ACKNOWLEDGMENTS) This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1D1A3B03030968). REFERENCES 1. Colebatch JG, Halmagyi GM. Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 1992;42:1635-6. 2. Lee YJ, Lee CG, Cho SH, Park YJ, Kim HJ, Lee KH, et al. Vestibular function test of dizziness patients by vestibular evoked myogenic potential. Res Vestib Sci 2012;11:37-43. 3. Murofushi T. Clinical application of vestibular evoked myogenic potential (VEMP). Auris Nasus Larynx 2016;43:367-76. 4. Roditi RE, Eppsteiner RW, Sauter TB, Lee DJ. Cervical ves- 47
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