Research in Vestibular Science Vol. 14, No. 1, March 2015 Review pissn 2092-8882, eissn 2093-5501 전정유발근전위의기본원리와방법 서울대학교병원이비인후과 이민영, 서명환 The Principle and Methodology of Vestibular Evoked Myogenic Potential Min Young Lee, Myung-Whan Suh Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea Received Feb 8, 2015 Revised Feb 11, 2015 Accepted Feb 15, 2015 Corresponding Author: Myung-Whan Suh Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: +82-2-2072-4845 Fax: +82-2-766-2447 E-mail: drmung@naver.com Copyright c 2015 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/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Vestibular evoked myogenic potential (VEMP) has developed as a broadly applied vestibular function test in clinics from its introduction in 1992. In the past, there was only one well known VEMP protocol, which is cervical VEMP, however recently ocular VEMP is also popular. Therefore, clarifying the VEMP recording protocol (cervical VEMP or ocular VEMP) before discussing the VEMP result has become essential. There is considerable difference regarding this VEMP test from other vestibular function tests. VEMP is thought to be assessing the functions of the otolith organs (utricle and saccule) which are evoked by acoustic stimulus. Cervical VEMP is valuable since this is the only available test method which could speculate the function of the saccule and inferior vestibular nerve. Still, there s less clearly understood part regarding the central pathway of VEMP. However, many clinicians and researchers participating in vestibular research speculate that this functional test will have a more dominant role in the near future. Here we describe the basic principles and methodological considerations regarding VEMP recording. Res Vestib Sci 2015;14(1):9-14 Keywords: Vestibular function tests; Saccule and utricle; Evoked potentials; Vestibular evoked myogenic potentials 서론전정유발근전위 (vestibular evoked myogenic potential, VEMP) 는 1992년 Colebatch와 Halmagyi 1 에의해처음기술되었다. 그이후이검사의사용은점차증가하여, 어지럼증검사중임상적으로중요한검사방법으로인정받고있다. 2 초기에는청각자극이후목의근육에서의억제성근전위반응인경부전정유발근전위 (cervical VEMP, cvemp) 에관하여주로연구가이루었지만, 최근에는유사한소리자극으로발생하는외안근에서의흥분성근전위반응인 외안근전정유발근전위 (ocular VEMP, ovemp) 에관한이해도도깊어지고, 관련연구도증가하고있다. 그러므로최근에는이제이검사를단순히 VEMP라고표기하는것은추후혼동을일으킬수있으며, 명확히 cvemp와 ovemp 를구분하여기술하는것이요구된다. 따라서임상의및연구자는이처럼두가지 VEMP 검사방법을정확하게이해하고사용하는것이필요할것으로생각되며, 이에저자들은 cvemp와 ovemp의기본원리와측정하는방법에대해기술하고자한다. 9
Res Vestib Sci Vol. 14, No. 1, Mar. 2015 본론 1. cvemp의기본원리기존연구들에의하면 cvemp의경우이석기관중구형낭 3 과하전정신경 4,5 의기능을반영한다고보고된다. 이중단일운동단위에서의측정결과에의하면, 청각자극 ( 소리또는진동 ) 에의해서근전도전기신호가일시적으로변동하는것을 cvemp 반응으로간주하였다. 6 대표적으로청성뇌간유발반응검사 (auditory brainstem evoked response) 와같은기존의유발반응검사는자극에의해활성화된여러신경유발전위가동기화되고합쳐진흥분반응을측정한다. 하지만 cvemp는일반적인유발반응검사와차별화된지속적인수축과정에있는근육의방해자극또는억제자극으로인해발생하는것으로알려져있다. 7 cvemp에서이용되는청각자극은선택적으로이석기관중하나를자극하는것으로알려졌다. 8,9 이는두 VEMP 방법모두에해당되는설명이다. 하지만최근에는이러한청각자극이이석기관뿐아니라반고리관의팽대부를동시에자극한다는주장과근거들이거론되기도하였다. 10,11 그러므로 VEMP가가능성이있는여러말초전정기관중어떤수용기를통하여어떤신경경로로전달되는지는아직명확하지않다. 그럼에도불구하고 cvemp의경우에는구형낭이수용기이며하전정신경이전달신경경로라는점은이견이적다. 2. ovemp의기본원리 ovemp는전정안반사의한종류로추측된다. 2 이러한 ovemp는기존의 cvemp와명확히대비되는부분들이있는데, 이는반대쪽외안근에서주된반응이관찰된다는점과흥분성반응이라는점이다. 단일운동단위측정결과에의하면, ovemp가발생하는기원은외안근중에하사근으로추정된다. 12 기존의다른연구에따르면하직근에서도반응이보고되기도하였으나, 하사근의반응보다늦은 ( 약 5 ms) 반응으로주된반응일가능성이떨어지며, 임상적으로측정되고있는 ovemp의경우에는하사근이그기원일것으로추측된다. 2 ovemp의그수용기와신경경로에관해서는아직까지이견이있다. 상전정신경염과하전정신경염환자들을기존의온도안진검사와회전의자검사를통해구분하여 ovemp 검사와비교한연구에서는 ovemp 전달경로는상전정신경일가능성이높았다. 13-16 최근에는세반고리관의기능을개별적으로평가할수있는두부충동검사 (video head impulse test) 가도입되었는데, 이결과를 ovemp 결과와비교한연구에서도상전정신경염환자들은외직근 VEMP의비정상결과가주로발견되었고, 하전정신경염환자들의경우에는 cvemp 비정상결과가주로발견되었다. 16 이상다수의연구보고들에의하면청각 ( 진동과소리 ) 자극을통한 ovemp는상전정신경을통한신경전달반응이라는것이주된의견이다. 2 하지만 ovemp의수용기가어느말초전정기관인지에관해서는명확하지않다. 상전정신경은이석기관중대부분난형낭 (utricle) 에서발생하는신호를전달한다. 따라서외직근 VEMP의경우에는난형낭이수용기일가능성이높다고여겨진다. 2 하지만구형낭에서의신호중구형낭의앞쪽갈고리부분에서시작되는신호는부분적으로상전정신경으로전달된다고알려졌으며, 이런독특한연결이외직근 VEMP와관련성이추측되고있지만아직까지명확한증거는없다. 17 구형낭이그위치상소리자극에더민감할것으로추측되며, 이러한사실때문에외직근 VEMP의발생이구형낭에서시작할가능성을완전히제외할수없다. 18 결론적으로아직까지 ovemp의기본발생기전은명확하지는않다. 하지만기존의연구보고들을토대로정리하면, 청각자극중진동을통한자극은수용기가난형낭이라고의견이좁혀지고있고이를소리를통한자극도동일한이석기관과신경통로를통한반응일것으로추측되고있다. 19 3. cvemp의측정방법 cvemp의경우다양한경부근육에서의측정이가능하다. 최근에는흉쇄유돌근에서의측정이가장보편적이다. 20 기본적으로 cvemp의경우억제반응을측정하는것이므로, 어느정도근육의기본적인수축이필요하다. 따라서 sternocleidomastoid (SCM) 를수축시키기위해다양한방법들이소개되고있다. 앉은자세에서머리를청각자극귀와는반대방향으로회전하는방법이있으며, 21,22 또한누운자세에서머리를바닥으로부터거상하는방법이있다. 23,24 혹은이두가지조합하여누운자세에서머리를회전하고추가로거상하는방법이가능하다. 이중어떠한방법을선택하더라도 SCM의수축이가능하다면 VEMP 반응을얻는것에는문제는없다. 하지만유의할부분은이근육의수축 10
이민영외 1 인. 전정유발근전위의기본원리와방법 Figure 1. Placement of surface electrode for cervical vestibular evoked myogenic potential (cvemp) and ocular VEMP (ovemp). (A) For the recording of cvemp, surface electrodes are placed mid-point of the sternocleidomastoid muscle (+ electrode: active electrode), sternoclavicular junction ( electrode: reference electrode), and the center of the forehead (ground electrode). (B) For the recording of ovemp, surface electrodes are placed mid-eye line below the contralateral eye (+ electrode: active electrode), 1 3 cm below the + electrode ( electrode: reference electrode), and the center of the forehead (ground electrode). 강도에의해 cvemp의크기가양의상관관계로증가하기때문에 23 좌우를번갈아가면서측정할경우 SCM 수축강도가좌우대칭이되어야한다는점이다. 물론서로다른방법으로좌우검사를시행하는것은바람직하지않다. 표면전극의부착방법은 3개의표면전극을이용하는것이전형적이다. 활성전극 (+) 은 SCM의중앙부분에, 비활성전극 ( ) 은동측흉골바깥부분에, 접지전극은이마가운데에부착한다 (Figure 1A). 활성전극과비활성전극의위치를반대로하여도반응의크기나속도에는차이가없으며, 이경우반응 wave에서 p13파와 n23파가전자와는반대로표시될것이다. 20 또한접지전극의위치도다양하며이를이마가아닌반대쪽 SCM에붙이는경우도있다. 자극으로는소리자극을사용하는것이보편적이다. 골전도진동자극, 25,26 전기적자극, 27,28 의료용망치등의사용을통한두드림자극 29 등가능한방법은다양하다. 소리자극을이용하는경우그종류로는클릭음 (click) 과 0.5 khz 순음이가장흔히사용된다. 클릭음은매우짧고 (0.1 ms) 모든주파수에서비슷한에너지크기를가진소리이다. 이 에반해, 0.5 khz 순음은해당주파수에만에너지가집중된소리자극이다. 이처럼 cvemp에특정주파수의순음이이용되는이유는인간의구형낭이소리를듣는것에특화된기관이아니므로역치가매우높으며 ( 약 85 95 db nhl) 가장민감한영역이약 0.5 khz 부근이기때문이다. 30 클릭음또는 0.5 khz 자극소리를이용하는경우두자극소리의결과에는큰차이가없지만순음자극의경우클릭음보다반응크기가약간크고역치가낮아지며잠복기 (latency) 가약간늘어난다고알려져있다. 31 보편적으로자극의빈도의경우 3 7 Hz, 소리자극의크기는 90 100 db nhl, sweep 수는 100 256번으로설정한다. 최근에는이검사의방법과해설에있어서국제적인권장기준이제시되었다 (Table 1). 32 cvemp의경우위에서기술한바와같이유의할부분이한가지있다. cvemp는경부근육수축의억제성반응이기때문에, 좌우반응을비교하고자하면경부근육수축강도가유사혹은동일해야한다. 이의대안으로 cvemp 검사시에근전도평균교정전위 (mean rectified voltage) 를측정하고 SCM 수축정도를동시에측정하여, 측정된반응 11
Res Vestib Sci Vol. 14, No. 1, Mar. 2015 Table 1. Recommended parameters of cervical vestibular evoked myogenic potential 32 Parameters Number of channels 1 or 2 Gain of amplifier 5,000 time Filter (low pass) 5 30 Hz Filter (high pass) 1,000 3,000 Hz Sampling rate 2,500 10,000 Hz Sweep time 100 ms Sweeps (n) 100 250 의진폭을 SCM 수축강도에비교해조절하는방법이이용된다. 하지만이방법의경우기본적인 VEMP 기계외에추가장비가필요하다는단점이있다. 혹은다른방법으로혈압계를이용하는방법이있다. 회전된턱을이용해손바닥에감아놓은혈압계커프를압박하게유도하여경부수축강도를간접적으로정량화하는방법도소개되었다. 33 하지만이방법역시팔근육의긴장도가변함에따라측정값이달라질가능성이있기때문에비효율적이라는보고도있다. 24 혹은측정직전에근육수축강도를매번측정하여, p13n23 진폭의크기를측정할때근육수축강도를보정하는방법도소개되었다. 34 이를 rectified VEMP라고명칭하며 Biologic사 (Claix, France) 에서 Navigator Pro 장비를통해이에해당하는알고리즘을제공한다. 이방법을검토한연구에의하면, 근육수축의비대칭정도가작은경우비대칭성의교정이가능하였지만, 35 비대칭성이큰경우한계가있었으며, 비대칭성이아주적은경우오히려큰편차를유발하는것으로보고되었다. 35 그러므로이러한비대칭성양측경부근육수축을보정할확실한대안은없으며, 측정할때양측경부근육의비대칭성이발생하지않도록노력하는것이바람직할것이다. 4. ovemp 의측정방법 ovemp는주로하사근의반응을측정하며이때문에전극을눈아래부분에부착하게된다. 활성전극 (+) 은눈바로아래정중선에, 비활성전극 ( ) 은그보다 1 3 cm 아래부착한다 (Figure 1B). 접지전극은마찬가지로이마가운데에붙인다. ovemp의경우에는반대방향으로정보가교차하므로자극의방향과전극의위치는반대방향에위치하게된다. ovemp의경우 cvemp에비하여그진폭이작고 (1/10), 발생률이적지만반응이동시에양측에서보일수 있다. 하지만동측에서의반응은크기가작은것으로알려진다. 36 cvemp는근육의수축방법과자세가중요하였지만, ovemp는이에반해흥분성반응이기에고려사항이흔치않다. 하지만최근보고에의하면앉은자세와누운자세에서진폭이다르다는결과가있었기때문에검사시에일정한자세를취하게하고각각의조건에서개별정상범위를측정하는것이추천된다. 37 ovemp는눈의주시방향에의해반응의크기가변하는것으로보고되고있다. 다양한주시방향으로실험한결과에서는눈의주시방향이시계방향으로 20 30도위쪽으로향하는경우가장큰진폭을얻었다. 37 이에대한설명으로는이러한상향주시할때하사근의위치가전극에가깝기때문으로추정된다. 19 이와는유사하게눈을움직이지않고정면을주시하고, 머리를숙여같은주시방향을유지하는것도가능하다. 38 소리자극은기존의 cvemp와크게다르지않으며, 즉 0.5 khz ( 연구자에따라 1 khz 39 ) 순음을주로사용하며크기는 100 110 db nhl ( 연구자에따라 120 130 db SPL 19 ), 자극의빈도는약 5 Hz로설정한다. Epoch의경우 50 100 ms, sweep수는 100 250번이추천된다. 38,40 진동, 골도자극의경우대게 0.5 khz 자극이사용되지만, 19 추가로고려할부분이있다. 일반적인순음청력검사에서사용되는골전도자극장치중대표적인 Radioear B-71은이의자극의강도가이석기관이난형낭 ( 수용체 ) 을충분히자극하지못한다는보고가있다. 19 특히이마가운데부위 (Fz 41 ) 에진동을가하는경우양측난형낭을모두자극하기는것이힘들다고보고된다. 42 대안으로이골전도자극장치를양측을각각따로측정하는것은조금더좋은결과를보일수있지만, 이경우에는자극의위치가조금만달라져도양측귀로전달되는에너지가바뀌기때문에결과의해석이어렵다. 41 따라서골진동기를이용한연구에서는 Minishaker 4810 (Bruel & Kjaer, Nærum, Denmark) 이주로사용된다. 43 결론 cvemp와 ovemp는소리, 진동등을이용한청각자극을이용하여전정기능을평가하는특별한검사이다. 그중 cvemp는구형낭의기능을반영하는검사로알려져있으며, 이검사외에다른전정기능검사로는구형낭의기능 12
이민영외 1 인. 전정유발근전위의기본원리와방법 평가가불가능하기에임상적으로의미가있다. ovemp의경우아직불분명한부분이존재하지만최근의많은연구에의해다양한정보들이밝혀지고있으므로, 긍정적인발전을기대해본다. 중심단어 : 전정기능검사, 구형낭과난형낭, 유발전위, 전정근유발전위 CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported. 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. Rosengren SM, Kingma H. New perspectives on vestibular evoked myogenic potentials. Curr Opin Neurol 2013;26:74-80. 3. Didier A, Cazals Y. Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig. Hear Res 1989;37:123-7. 4. Robertson DD, Ireland DJ. Vestibular evoked myogenic potentials. J Otolaryngol 1995;24:3-8. 5. Murofushi T, Matsuzaki M, Mizuno M. Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 1998;124:509-12. 6. Colebatch JG, Rothwell JC. Motor unit excitability changes mediating vestibulocollic reflexes in the sternocleidomastoid muscle. Clin Neurophysiol 2004;115:2567-73. 7. Wit HP, Kingma CM. A simple model for the generation of the vestibular evoked myogenic potential (VEMP). Clin Neurophysiol 2006;117:1354-8. 8. 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. 9. Murofushi T, Curthoys IS. Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig. Acta Otolaryngol 1997;117:66-72. 10. Xu Y, Simpson I, Tang X, Zhou W. Acoustic clicks activate both the canal and otolith vestibulo-ocular reflex pathways in behaving monkeys. J Assoc Res Otolaryngol 2009;10: 569-77. 11. Zhu H, Tang X, Wei W, Mustain W, Xu Y, Zhou W. Click-evoked responses in vestibular afferents in rats. J Neurophysiol 2011;106:754-63. 12. Weber KP, Rosengren SM, Michels R, Sturm V, Straumann D, Landau K. Single motor unit activity in human extraocular muscles during the vestibulo-ocular reflex. J Physiol 2012;590:3091-101. 13. Manzari L, Tedesco A, Burgess AM, Curthoys IS. Ocular vestibular-evoked myogenic potentials to bone-conducted vibration in superior vestibular neuritis show utricular function. Otolaryngol Head Neck Surg 2010;143:274-80. 14. 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. 15. Govender S, Rosengren SM, Colebatch JG. Vestibular neuritis has selective effects on air- and bone-conducted cervical and ocular vestibular evoked myogenic potentials. Clin Neurophysiol 2011;122:1246-55. 16. Shin BS, Oh SY, Kim JS, Kim TW, Seo MW, Lee H, et al. Cervical and ocular vestibular-evoked myogenic potentials in acute vestibular neuritis. Clin Neurophysiol 2012;123: 369-75. 17. Isu N, Graf W, Sato H, Kushiro K, Zakir M, Imagawa M, et al. Sacculo-ocular reflex connectivity in cats. Exp Brain Res 2000;131:262-8. 18. Govender S, Colebatch JG. Ocular vestibular evoked myogenic potential (ovemp) responses in acute vestibular neuritis. Clin Neurophysiol 2012;123:1054-5; author reply 5-6; discussion 6-7. 19. Curthoys IS, Vulovic V, Manzari L. Ocular vestibular-evoked myogenic potential (ovemp) to test utricular function: neural and oculomotor evidence. Acta Otorhinolaryngol Ital 2012;32: 41-5. 20. Suh MW, Jeong SH, Kim JS. Vestibular evoked myogenic potential: recording methods and clinical application. J Korean Neurol Assoc 2010;28:1-12. 21. Ochi K, Ohashi T, Nishino H. Variance of vestibular-evoked myogenic potentials. Laryngoscope 2001;111:522-7. 22. 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;141:180-8. 23. Wang CT, Young YH. Comparison of the head elevation versus rotation methods in eliciting vestibular evoked myogenic potentials. Ear Hear 2006;27:376-81. 24. Suh MW, Kim JS, Koo JW. Influence of blood pressure manometer feedback on the parameters of the vestibular evoked myogenic potential test. Ann Otol Rhinol Laryngol 2009;118: 281-6. 25. Sheykholeslami K, Habiby Kermany M, Kaga K. Frequency sensitivity range of the saccule to bone-conducted stimuli measured by vestibular evoked myogenic potentials. Hear Res 2001; 160:58-62. 26. Sheykholeslami K, Habiby Kermany M, Kaga K. Bone-conducted vestibular evoked myogenic potentials in patients with congenital atresia of the external auditory canal. Int J Pediatr Otorhinolaryngol 2001;57:25-9. 27. Monobe H, Murofushi T. Vestibular testing by electrical stimulation in patients with unilateral vestibular deafferentation: 13
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