Research in Vestibular 이선욱 Science. 뇌줄기 Vol. 뇌졸중으로 20, No. 1, 인한 March 어지럼증 2021 Review pssn 2092-8882, essn 2093-5501 https://doi.org/10.21790/rvs.2021.20.1.1 뇌줄기뇌졸중으로인한어지럼증 이선욱 1,2 1 고려대학교안암병원신경과, 2 서울대학교의과대학신경과학교실 Vascular Origin of entral Vertigo: Brainstem Sun-Uk Lee 1,2 1 Department of Neurology, Korea University Medical enter, Seoul; 2 Department of Neurology, Seoul National University ollege of Medicine, Seoul, Korea Received Nov 19, 2020 Revised Feb 5, 2021 Accepted Feb 17, 2021 orresponding Author: Sun-Uk Lee Department of Neurology, Korea University Anam Hospital, Korea University ollege of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Korea Tel: +82-2-2286-6262 Fax: +82-2-925-2472 E-mail: sulee716@gmail.com ORD: https://orcid.org/0000-0001-8660-7759 opyright c 2021 by The Korean Balance Society. All rights reserved. This is an open access article distributed under the terms of the reative ommons Attribution Non-ommercial 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. Various neurotologic findings can be observed in stroke involving the brainstem. Analyses of the neurotologic findings are important in brainstem stroke since it can have negative diffusion-weighted image, as well as, presenting with acute vestibular syndrome in isolation without any associated neurologic deficits. n this review we discuss the neurotologic findings from lesion involving (1) the medial vestibular nucleus, (2) nucleus prepositus hypoglossi, (3) inferior cerebellar peduncle, (4) medial longitudinal fasciculus, (5) rostral interstitial nucleus of the medial longitudinal fasciculus, (6) interstitial nucleus of ajal, and (7) middle and (8) superior cerebellar peduncles. t is important to recognize these specific neurotologic findings depending on the neural structures involved that may guide early detection and proper management. Res Vestib Sci 2021;20(1):1-6 Keywords: Nystagmus; entral vertigo; Brainstem 서론 갑작스럽게발생하며 24시간이상지속되는회전성어지럼증이주된증상인급성전정증후군 (acute vestibular syndrome) 은대개전정신경염을위시한말초성전정병변으로인해발생하나, 뇌줄기나소뇌같은후방순환영역뇌졸중 (posterior circulation stroke) 에의해서도종종나타날수있어진단에주의를요한다. 실제로, 후방순환영역뇌졸중환자중 62% 는적어도한차례이상의급성어지럼 증을경험하며, 후방순환영역뇌졸중초기증상의 19% 는급성어지럼증이다 [1,2]. 후방순환영역의뇌졸중은국소적신경학적이상없이급성어지럼증단독으로발현할수있으며, 뇌혈관이상에의한어지럼증의영상학적진단정확도는 35% 로매우낮다 [3-6]. 특히뇌줄기에는안구운동을담당하는뇌신경및신경핵들이밀집해있어, 뇌줄기를침범하는뇌졸중의경우각종안진및안구운동장애가흔하게관찰되므로이를정확하게해석하고진단하는것이중요하다 [7,8]. 이종설에서는뇌줄기의국소 1
Res Vestib Sci Vol. 20, No. 1, Mar. 2021 병변으로 인해 나타날 수 있는 신경이과 소견에 대해 정 (dorsolateral portion)에 위치한다(Fig. 1). 내측전정핵은 말 리하고자 한다. 초 전정신경의 정보가 교차하는 부위로, 해당 부위가 손 상되면 말초성 및 중추성 전정기능 장애가 혼재해 나타나 본 론 게 된다[7]. 즉 병변 반대편으로의 자발안진, 병측으로의 두부충동검사 양성 소견을 보이거나 온도안진검사에서 신경구조물에 따른 눈운동 이상을 Table 1에 간략히 정 반고리관 마비(canal paresis)를 보일 수 있어, 말초신경병 리하였다. 증으로 쉽게 오인될 수 있다(pseudo-vestibular neuritis). 하 지만 전정신경염과는 달리 비디오 두부충동검사나 자기 1. 내측전정핵(medial vestibular nucleus) 추적 코일(magnetic search coil)에서 병측 뿐 아니라 건측 수평 및 후반고리관의 전정안반사 이득이 감소된 양상을 보인다. 이는 내측전정핵 손상에 따른 건측으로의 억제성 전정핵은 꼭대기쪽 연수와 바닥쪽 교뇌의 등가측 부위 Table 1. Neurotologic findings in patients with brainstem lesions Variable Spontaneous nystagmus Gaze-evoked nystagmus Bithermal caloric tests Video head-impulse tests OTR/SVV a) MVN NPH P MP SP MLF + B (H, P) + (H) or + B or Dissociated torsional-vertical or hemiseesaw nystagmus + or (P) MVN, medial vestibular nucleus; NPH, nucleus prepositus hypoglossi; P, inferior cerebellar peduncle; MP, middle cerebellar peduncle; SP, superior cerebellar peduncle; MLF, medial longitudinal fasciculus;, contralesional;, ipsilesional; B, bilateral; H, horizontal canal; P, posterior canal; OTR, ocular tilt reaction; SVV, subjective visual vertical. a) Neural substrates of the midbrain are not indicated since those present mostly with supra- or infranuclear ophthalmoplegia. Fig. 1. Neural substrates responsible for eye movements in pons and medulla. HN, hypoglossal nucleus; MLF, medial longitudinal fasciculus; LVN, lateral vestibular nucleus; AN, abducens nucleus; MVN, medial vestibular nucleus; P, inferior cerebellar peduncle; VN, inferior vestibular nucleus; NPH, nucleus prepositus hypoglossi. 2
이선욱. 뇌줄기뇌졸중으로인한어지럼증 사이신경원 (interneuron) 도기능이저하되며, 이에대한적응기제로양측의전정안반사이득이감소한것으로설명한다 [9]. 또한내측전정핵은설하전신경핵과더불어, 뇌줄기에서수평면의신경적분체 (neural integrator) 로기능한다 [10]. 가측주시시에안와에존재하는인대와근육에의한복원력에의해안구에는다시정위로돌아가려는복원력이작용하게된다. 신경적분체들은전운동신경원 (premotor neuron) 으로부터전달받은속도정보를적분하여안구움직임의목표지점의위치정보를안구운동신경원으로산출해주는중개역할을하여, 가측주시시안구가중심으로끌려가지않고목표점에원하는만큼머무를수있게한다. 따라서, 내측전정핵을포함한신경적분체에병변이발생하면수평주시유발안진 (gaze-evoked nystagmus) 이발생하며 [11], 이경우안진서상의파형 (waveform) 은대개특징적으로감소서상 (decelerating slow-phase velocity) 의양상을띤다. 안구기울임반응및주관적시축검사는대개내측전정핵병변에서정상소견을보인다 [11]. 2. 설하전신경핵 (nucleus prepositus hypoglossi) 설하전신경핵은내측전정핵, 소뇌타래엽 (flocculus) 와함께수평방향의신경적분체로기능하며교뇌-연수접합부의등측및내측전정핵의내측에위치한다 (Fig. 1). 설하전신경핵은올리브핵, 소뇌타래엽을거쳐반대편의내측전정핵에흥분성날신경 (efferent) 신호를전달하며, 따라서이부위에병변이생기면병변측소뇌타래엽및반대편전정핵의기능이저하된다 [12]. 따라서설하전신경핵의병변은수평성주시유발안진외에병변측으로의자발안진및건측으로의두부충동검사이상을보이나, 온도안진검사는정상소견을보인다 [9,12]. 안구기울임반응및주관적시축비틀림은병변측이나병변반대편으로비슷한빈도로관찰된다 [12]. 전정감각들을소뇌에서통합하는데, 아래소뇌다리에뇌졸중이발생하면급성전정신경병증이발현할수있다. 통상적으로아래소뇌다리병변에서보이는신경안과적소견은병측으로의자발안진과체측방돌진 (body lateropulsion), 병변반대편으로의주관적시축비틀림및안구기울임반응이특징적이다 [14]. 최근의연구에서원지성 (apogeotropic) 중추성체위안진이발생할수있다고보고하였으며, 이는소뇌결정결절 (nodulus) 나전방목젖 (uvula), 편도 (tonsil) 로의날신경섬유들의침범으로인해발생한다고추측된다 (Fig. 2) [15]. 4. 안쪽세로다발 (medial longitudinal fasciculus) 동안신경과외전신경을연결해주는안쪽세로다발에병변이생기면핵사이안근마비 (internuclear ophthalmoplegia) 가발생한다. 핵사이안근마비환자에서병변측내전장애 (adduction limitation) 및병변반대편주시시에외전안에서해리성외전안진 (dissociated abducting nystagmus) 이관찰되는것이특징적이다 [10]. 이러한해리성안진이나타나는기전은내직근마비를보상하기위한신경발화의증가가헤링의법칙 (Hering s law of equal innervation) 에의해반대편외직근에도같이전달되기때문으로생각되어왔다. 하지만, 최근연구에의하면내직근마비로인해발생하는외전안의속도정보 (pulse) 와위치정보 (step) 간의부조화 (pulse-step mismatch) 로인해해리성안진이발생한다고하였다. 즉, 안구장애에대한적응기제로정중곁교뇌그물체 (paramedian pontine reticular formation) 의 pulse discharge가증가하는데반해 step signal은불변함으로써해리성안진이발생하며 [16,17], 이러한연유에서안진보 3. 아래소뇌다리 (inferior cerebellar peduncle) 뇌줄기와소뇌는 3개의소뇌다리를통해연결되는데, 아래소뇌다리는등측척수소뇌로 (dorsal spinocerebellar tract) 로서, 올리브핵및전정핵으로부터의소뇌의날신경섬유들이아래소뇌다리를통해주행한다 [13]. 이섬유들을통해전달되는고유감각 (proprioceptive), 체성감각및 Fig. 2. Neural connection between the nodulus (N) and vestibular nuclei complex (VN). P, inferior cerebellar peduncle. 3
Res Vestib Sci Vol. 20, No. 1, Mar. 2021 다는속진 (saccadic intrusion) 에합당한안구운동이상으로간주되기도한다. 드물게반시소안진 (hemiseesaw nystagmus) 이나, 수직방향의해리안진이관찰되기도한다. 전자는양측눈의회선성분은공액성으로움직이나, 수직성벡터는반대방향의안진이관찰되는경우를말한다. 후자는한쪽눈에서는수직안진이, 반대편눈에서는회선안진이주로관찰되는경우로, 이러한안진들은전방및후방고리관의전정안반사로가선택적으로침범함으로써발생하는것으로알려져있다 [18,19]. 안쪽세로다발병변에서는눈기울임반응 (ocular tilt reaction) 이흔하게발생하는데, 이는중력감지로 (graviceptive pathway) 가안쪽세로다발을통해주행하기때문이다 [20,21]. 이에대해서는뒤에서다시설명하기로한다. 5. 안쪽세로다발입쪽사이질핵 (rostral interstitial nucleus of the medial longitudinal fasciculus) 안쪽세로다발입쪽사이질핵은중뇌의위둔덕 (superior colliculus) 높이에서뇌간의정중선의내측및중뇌수도관 (aqueduct) 배측에위치한다 (Fig. 3). 안쪽세로다발입쪽사이질핵의병변은대개덮개앞증후군 (pretectal syndrome) 의일부로상방주시마비가흔하게관찰된다 [10,22]. 환자들 은신속안구운동이나원활추종운동같은의도적 (volitional) 안구운동을통해서는상방주시가불가능한데반해, 수직전정안반사에의해서는안구마비가극복되는특징적인핵위마비 (supranuclear palsy) 의양상을보인다. 눈모음 (convergence) 도대부분가능치않으며, 카할사이핵병변에서는동측으로향하는회선자발안진이보이는데반해 [23], 안쪽세로다발입쪽사이질핵에서는반대편으로향하는안진이관찰된다 [24]. 6. 카할사이핵 (interstitial nucleus of ajal) 카할사이핵은수직면과회선성주시유지에신경적분체로서중요한역할을하며병변이생길경우수직면의주시유발안진이발생한다. 뇌졸중은대부분카할사이핵의일측성기능이상을유발하는데, 이로인해동측으로의회선안진및머리기울임 (head tilt) 반응이유발될수있다. 머리기울임반응이발생하는원리는다음과같다. 머리를한쪽으로기울이면동측의타원낭 (utricle) 및전방및후방반고리관이자극되는데, 이로인해동측안구의상사근, 상직근, 반대편의하사근과하직근을흥분시켜, 고개를기울인쪽의안구는내회선및상전, 고개를기울인반대편의안구는외회선및하전이발생하게된다. 눈기울임반응은이러한중력감지로의이상이생길경우 Fig. 3. Neural substrates responsible for eye movements in the brainstem. N, interstitial nucleus of ajal; MLF, medial longitudinal fasciculus; rimlf, rostral interstitial nucleus of the MLF;, oculomotor nucleus; V, trochlear nucleus; V, abducens nucleus. 4
이선욱. 뇌줄기뇌졸중으로인한어지럼증 발생하는데, 이는전방및후방반고리관과타원낭에서부터시작되어관상회전면 (roll plane) 의전정안반사를관장하는동안신경, 활차신경핵을거쳐반대편카할사이핵및안쪽세로다발입쪽사이질핵에다다르는경로어디에서건병변이생기면발생할수있다 [25]. 눈기울임반응은머리기울임, 스큐편위 (skew deviation), 안구회선 (ocular torsion) 의 3가지반응으로이루어지며, 말초전정및하부뇌간병변에서는병변쪽으로눈기울임반응이발생하고, 상부뇌간병변에서는병변반대편으로발생한다 [26]. 눈기울임반응은 3가지현상이모두관찰될수도있으나, 환자에따라서는일부만나타나는경우도흔하다. 7. 중간소뇌다리 (middle cerebellar peduncle) 중간소뇌다리는전하소뇌동맥 (anterior inferior cerebellar artery) 이혈류를공급하는데, 미로에혈류를공급하는미로동맥또한전하소뇌동맥으로부터분지되어총와우동맥 (common cochlear artery) 과앞전정동맥 (anterior vestibular artery) 을내게된다 [27]. 이러한이유로전하소뇌동맥경색에서는흔하게미로도허혈성손상을받게되며중간소뇌다리뇌졸중에서는급성청력저하외에도전정의손상에따른말초성전정병증이같이동반한다 [28]. 전하소뇌동맥은소뇌타래에도혈류를공급하는데, 경우에따라선소뇌타래침범에따른중추성안진과미로손상에의한말초성안진이혼합되어나타날수있어해석에주의를요한다 [9,29]. 8. 위소뇌다리 (superior cerebellar peduncle) 위소뇌다리에는소뇌로부터적핵 (red nucleus), 시상및시상하부, 교뇌그물체, 올리브핵에이르는대부분의소뇌들신경섬유 (afferent fibers) 들이주행하지만, 배측척수소뇌로 (ventral spinocerebellar fiber) 같은일부날신경섬유들도위소뇌다리를거쳐뇌줄기및대뇌로향하게된다. 바닥쪽소뇌와달리꼭대기쪽소뇌는안구운동에는크게관여하지않는것으로알려져있어위소뇌다리병변에서도특별한눈운동이상은보이지않으나, 일부환자에게서동측으로의체측방돌진및눈기울임반응, 중추성체위안진을보일수있다고알려져있다 [30,31]. 결 뇌줄기에는안구운동을담당하는뇌신경이밀집되어있어여러양상의눈운동이상및안진이다양하게나타난다. 뇌줄기에허혈성병변이발생하는경우자기공명영상에서정상을보이는경우도있으며, 다른신경학적증상이나징후없이급성전정증후군단독으로발현할수있다. 또한뇌줄기병변으로인해말초성및중추성안진이혼합되어나타날수있기때문에해석에유의해야한다. 따라서앞에서열거한특정신경학적구조물침범에따른눈운동의양상을이해하는것이중추성어지럼증을진단하는데있어중요하다하겠다. 론 중심단어 : 안진, 중추현훈, 뇌줄기 이해관계 (ONFLT OF NTEREST) 저자는이논문과관련하여이해관계의충돌이없음을명시합니다. REFERENES 1. Grad A, Baloh RW. Vertigo of vascular origin: clinical and electronystagmographic features in 84 cases. Arch Neurol 1989; 46:281-4. 2. Paul NL, Simoni M, Rothwell PM; Oxford Vascular Study. Transient isolated brainstem symptoms preceding posterior circulation stroke: a population-based study. Lancet Neurol 2013; 12:65-71. 3. Kerber KA, Brown DL, Lisabeth LD, Smith MA, Morgenstern LB. Stroke among patients with dizziness, vertigo, and imbalance in the emergency department: a population-based study. Stroke 2006;37:2484-7. 4. hoi JH, Park MG, hoi SY, Park KP, Baik SK, Kim JS, et al. Acute transient vestibular syndrome: prevalence of stroke and efficacy of bedside evaluation. Stroke 2017;48:556-62. 5. Tarnutzer AA, Lee SH, Robinson KA, Wang Z, Edlow JA, Newman-Toker DE. ED misdiagnosis of cerebrovascular events in the era of modern neuroimaging: a meta-analysis. Neurology 2017;88:1468-77. 6. Newman-Toker DE, Saber Tehrani AS, Mantokoudis G, Pula JH, Guede, Kerber KA, et al. Quantitative video-oculography to help diagnose stroke in acute vertigo and dizziness: toward an EG for the eyes. Stroke 2013;44:1158-61. 7. Lee SU, Park SH, Park JJ, Kim HJ, Han MK, Bae HJ, et al. Dorsal medullary infarction: distinct syndrome of isolated central vestibulopathy. Stroke 2015;46:3081-7. 5
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