REVIEW J Neurocrit Care 2016;9(2): eissn 급성발작에의해발생하는뇌병변 권오영 유상경 김영수경상대학교의학전문대학원신경과학교실, 건강과학연구원 Brai

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1 REVIEW J Neurocrit Care 2016;9(2):78-91 eissn 급성발작에의해발생하는뇌병변 권오영 유상경 김영수경상대학교의학전문대학원신경과학교실, 건강과학연구원 Brain Lesions Attributed to Acute Seizures Oh-Young Kwon, MD, PhD, Sang Kyeong Yoo, MD, and Young-Soo Kim, MD, PhD Department of Neurology and Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Korea Brain lesions may be detected by magnetic resonance imaging (MRI) during acute seizures or just after the seizures. Lesions are associated with restriction of diffusion, increment of T2 signals, and increment of contrast enhancement (CE) in MRI. Magnetic resonance angiography (MRA) and brain perfusion images are useful for distinguishing brain lesions attributed to acute seizures (BLASs) from acute ischemic lesions. BLASs can be distinguished from acute cerebral infarction with the following features. MRA may indicate that cerebral blood vessels in the regions of BLASs are prominent or have an increased diameter. A distinct emergence of vascular branches may also be observed at the regions in MRA. In addition, the early break-down of blood brain barrier in the BLASs and their surrounding areas may lead to CE of leptomeninges. Increase of local perfusion during the ictal phase also makes BLASs different from acute cerebral infarction. The differentiation of BLASs from other pathological conditions such as cerebral infarction and encephalitis is not straightforward. Misinterpretation of brain imaging may lead to failure to provide adequate managements or overuses of diagnostic methods and overtreatments. To reduce these clinically critical errors, we must have a multidisciplinary approach to diagnose patients conditions. Most BALSs are transient and reversible. Thus, follow-up studies of MRI are needed to confirm the lesions. However, the duration of the existence of the lesions are variable. Some lesions may remain while other may not. J Neurocrit Care 2016;9(2):78-91 Key words: Seizures; Magnetic resonance imaging; Physiopathology; Diagnosis Received October 31, 2016 Revised December 14, 2016 Accepted December 14, 2016 Corresponding Author: Oh-Young Kwon, MD, PhD Department of Neurology, Gyeongsang National University School of Medicine, Jinju-daero, Jinju 52727, Korea Tel: Fax: mnkwon21@hanmail.net Copyright 2016 The Korean Neurocritical Care Society 서론 뇌MRI (brain magnetic resonance imaging) 가널리보급되어응급실에서도뇌MRI를촬영하는것이흔한일이되었다. 따라서발작이발생하여응급진료를받는환자들에게도뇌MRI를빠르게검사할수있게되었다. 뇌MRI의민감도도증가하였다. 따라서뇌MRI에서뇌병변이관찰되는민감도낮았던시절에비해서발작에의해뇌에발생하는병적인변화를쉽게관 찰할수있게되었다. 개선된뇌MRI의해상도는병변의성격을더자세하게파악할수있게해주었다. 이런변화의영향으로발작을하는도중이나발작을한직후에뇌MRI를촬영하고그전에는쉽게보지못했던발작의급성기에발생하는뇌병변을의사들이잘관찰할수있게되었다. 그결과로발작에의해발생하는급성뇌병변에대한뇌MRI 영상소견이많이보고되고지식이축적되었다. cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 78

2 Oh-Young Kwon, et al. Brain lesions attributed to acute seizures 뇌MRI에서관찰되는급성발작뇌병변은뇌에병적으로수분환경이변하여나타나는소견으로발생하는부위의범위가넓게분포한다. 따라서수분환경의변화에민감한 MRI기술을이용하면병변을관찰하기가좋다. 발생하는병변은대개뇌부종으로판단하지만꼭그렇지는않다. 더구나발작이뇌세포에어떤변화를일으켜뇌MRI의신호에변화를일으키는지는아직설명하지못하는부분이많다. 발작의급성기에발생하는뇌병변을뇌MRI에서관찰하면다른원인에의해발생하는뇌병변과비슷한측면을가지고있어서, 뇌염, 뇌경색, 뇌종양등의병터들과혼돈되기도쉽다. 급성기에병변이감별이되지않아발작을일으킬수있는다른병변을급성발작뇌병변 (brain lesions attributed to acute seizures) 으로오인하면환자에게필요한치료를하지않아임상경과에영향을줄수가있다. 그와반대로발작에의해발생한병변을발작을유발하는다른병변으로오인하면환자에게지나친치료와검사를하게된다. 1-3 저자는급성발작뇌병변에대해임상적으로도움이되는정보를정리하고자한다. 본론 1. 병태생리 1) 병태생리의개요발작의급성기에발생하는뇌의병변은신경활성이증가하여발생한다. 이병변은또한신경활성이증가되어나타나는대사반응과혈관의반응과관련이있다. 이러한병변을병태생리적인면으로보면부종일가능성이많지만확정적으로판단하기는어렵다. 따라서이전의보고들에서도직접적인병태생리적표현을피하는것같다. 특히발작활성이있는장소에서동떨어진곳에발생하는병변에대해서는아직그병태생리학적인기전을잘모르고있다. 2) 대사장애와생화학적변화급성발작뇌병변은발작에의해뇌에발생하는대사와에너지요구량의변화와도관련이있다. 발작활성이지속되면뇌세포가당을더욱많이사용하게된다. 발작활성이있을때혈류가증가되지만뇌세포가사용하는당의양을따라가지못한다. 2,4,5 시간이지나고당을많이사용하여세포안에있는에너지저장고가부족하게되면 Na + /K + ATP 펌프가제대로작동하지않는다. 발작이발생하면글루탐산염이분비되어흥분독성 효과를나타내는데, 펌프가작동하지않으면상황은더욱나빠진다. 분비된글루탐산염은 NMDA수용체에작용하여칼슘과물을세포안으로흘러들어가게된다. 이러한과정에의해세포외액이감소하면뇌MRI에서확산이제한되어있는것을관찰할수있다. 5 뇌경색에서는초기에에너지실패가발생한다. 반면에뇌전증지속상태가진행하는동안에는과도한활성에의한손상과세포독성부종이뇌세포에발생하고, 시간이좀더경과하고나서뇌세포의에너지가결핍된다. 따라서뇌세포에서수분의확산이제한되는병태생리가급성발작병변과급성뇌경색사이에다르다. 뇌전증지속상태가진행되고있는상태에서급성발작병변이발생하면확산강조영상과 T2강조영상에서신호의변화가거의동시에발생한다. 반면에급성뇌경색에서는뇌조직에서수분의확산이제한되는것이 T2신호의이상이나타나는것보다앞서는일이자주있다. 자기공명분광법은발작과연관되어발생하는세포의대사산물의변화와에너지요구량의변화를감지한다. 양성자자기공명분광법은발작직후에뇌세포에젖산의농도가증가하는것을보여준다. 6,7 뇌조직에서 ph가변하고에너지에의존하는대사산물이변하면이변화를인자기공명분광법을사용하면감지할수있다. 7-9 자기공명분광법에의해관찰한 N-acetylaspartate (NAA) 는경우에따라결과가달랐다. NAA는발작직후에감소된것이기술되기도하였고. 10 증가된것이기술되기도하였다. 11 NAA가증가된것은신경세포가과다하게흥분한것을의미할수있지만, 반면에 NAA는발작직후에신경세포가기능이저하된것을의미할수있다. 발작직후에는신경세포가흥분하고흥분한후에기능이저하되는역동적인변화가일련적으로발생하기때문에관찰하는시기의약간의차이에의해서반대적상황이관찰될수있을것같다. 3) 뇌부종의증거급성발작뇌병변이발생하는기전은이론적모델과실험연구를통해서파악할수있었다. 뇌MRI에서관찰되는급성발작뇌병변을설명하는병리학적인증거가제시되기는했지만아직많지는않다. 동물연구의급성발작뇌병변에서수상돌기와별아교세포의부기가관찰되었다. 12 급성발작병변을생검한증례에서도신경아교증과세포부종이관찰되었고염증은없었다 뇌MRI를이용한동물실험은급성발작뇌병변이뇌부종이라는증거를보여주었다. 발작이발생한뇌의국소부위에서신경세포의이상이시작되면신경세포는붓고세포외액의양은변동이심해진다. 따라서뇌구조물의용적이일시적으 79

3 A B C D E F Figure 1. Lesions of seizure induced brain edema in a 64-year-old male. MRI and MR angiography were performed 3 days after serial attacks of complex partial seizure with secondary generalization (A, B, C, D, and E). High signal intensities were seen around the cortical area of the medial portion of the right superior frontal gyrus (arrow, upper line) and the cortical area of the precentral gyrus of the right hemisphere (arrow head, lower line) in DWI (A). In FLAIR images, the high signal intensities were much more prominent in the subcortical areas than those in the cortical areas (arrow and arrow head) (B). In ADC maps, the cortical lesions were observed in low signal intensities while the subcortical lesions were observed in high signal intensities (arrow and arrow head) (C). The lesions were partially enhanced (arrow and arrow head) in T1-weighted images with contrast enhancement (D). Diameter of the right anterior cerebral artery was dilated (arrow and arrow head) compared to that of the left anterior cerebral artery in MR angiographies (E). The lesions disappeared in the MRI performed one and half months later (F). MRI: magnetic resonance imaging; MR angiography: magnetic resonance angiography; DWI: diffusion-weighted images; FLAIR: fluid attenuated inversion recovery images; ADC: apparent diffusion coefficient. Adapted from Yang et al. J Korean Neurol Assoc 2015;33(1):54-56, with permission of Korean Neurological Association. 70 로증가하는뇌부종이발생한다. 이런변화는 T2강조영상 (T2 weighted image) 의신호강도를증가시킨다. 16,17 확산강조영상에서는겉보기확산계수 (apparent diffusion coefficient) 의변동이발생한다. 6 4) 신경손상조직학적인현상이가장잘밝혀져있는경우가급성뇌경색이다. 급성뇌경색이발생하였을때뇌조직에서수분의확산이제한된상태는뇌세포에신경독성부종이발생하였고영구적으로손상되었다는것을의미한다. 그러나발작에의해발생하는급성병변에서는급성뇌경색의병변과같은소견이영상에서보여도회복되는경우가많다. 따라서발작과연관된급성병변은세포사에도달하지않는경우가많다. 18 급성발작병변을생검한증례에서신경세포사멸이있다는증거를제시한증례들도있다. 19 5) 병변의유발요인뇌MRI에서관찰할수있는급성발작뇌병변이발작을경험하는모든환자에서발생하는것은아니다. 급성발작뇌병변이보고된증례들은대개뇌전증지속상태가있거나발작이무리를지어발생한경우이다. 그러나발작이한번만발생한후에 급성발작뇌병변이발생한증례들이보고되어있다. 12,14,20-23 뇌 MRI에서발견되는급성발작뇌병변은뇌전증지속상태가국소적으로발생하고일정한기간동안에만분명하게나타난다. 이병변은몇일혹은몇주동안만분명한데이는발작지속시간과강도의임계치가있어서그이하로발생할경우에는이런변화가발생하지않을것이라는것을시사한다. 4,13 발작지속시간과발작강도외에다른변수들로병변을유발하는데역할이있다. 이변수에는발작의형태와위치, 약물사용, 환자의연령, 동시에존재하는질환, 심혈관계기능과대사계기능의비축상태등이포함된다. 적은수이기는하지만일련의환자를묘사한보고에서, 뇌MRI에서관찰되는수분의확산제한은안쪽측두엽병소보다는새겉질에좀더잘발생하였다 병변의다양성급성발작뇌병변은발작중에뇌전증모양파가발생한부위에주로발생하는데, 뇌MRI 에서나타나는소견은다양하다. 2-5,12-15,20-22,24-31 부종이발생한다는증거로덩어리효과와구감쇠 (s ulc al effacement) 나이랑음영소실 (effacement of sulci and gyral markings) 과같은양상이나타날수가있는데특히해마가붓는경우가자주있다. 급성발작뇌병변의국소겉질부위를뇌 MRI에서관찰하면 T2강조신호가증가하고뇌조직에수분의 80

4 Oh-Young Kwon, et al. Brain lesions attributed to acute seizures A E B C D Figure 2. Brain MRI and MR angiography in a 66-year-old female with acute serial seizures of unknown types. Diffuse cortical edemas were observed along cortical area of the left hemisphere on FLAIR study (A). Same patterns were disclosed on the DWI (B). There was nothing special in ADC study (C). Note the vascular enhancement along the lesions on the enhancement study of T1-weighted study despite early stage of pathology (D). There was no difference in cerebral vascularity between bilateral hemispheres despite wide spread lesions in the left hemisphere (E). MRI: magnetic resonance imaging; MR angiography: magnetic resonance angiography; DWI: diffusion-weighted images; FLAIR: fluid attenuated inversion recovery images; ADC: apparent diffusion coefficient. 확산이 제한된다 (Table 1, Fig. 1 and 2). 뇌조직에 수분의 확산 진 부위에서 발생하기도 한다. 뇌전증활성이 있었던 부위 떨 이 제한되면 확산강조영상 (diffusion weighted imaging)에 밝 어진 원위부에 발생하는 병변은 교차소뇌기능해리(crossed 은 신호가 나타나고, 겉보기확산계수지도 (apparent diffusion cerebellar diaschisis), 같은 쪽사이뇌기능해리 (ipsilateral coefficient maps)에서는 어두운 신호가 나타난다 (Table 1). 때 diencephalic diaschisis), 뇌량팽대병변(lesions on splenium 로는 병변이 급성기 동안에 장소를 이동하기도 한다. of corpus callosum), 가역뒤뇌병증후군 (reversible posterior 언뜻 생각해보면 다소 이상하기도 하지만 발작의 급성기 leukoencephalopathy) 들이다. 에 뇌전증모양파가 발작에 의해 발생하는 급성병변은 뇌전 증모양파가 발생하는 부위에 발생한 부위에서 거리가 떨어 81

5 Table 1. Features of brain edema attributed to acute seizures in various modalities of brain magnetic resonance imaging Modality Features T2 weighted image Cortical and subcortical high signal T1 weighted image Cortical and subcortical low signal, Increased vascular enhancement Diffusion weighted image Cortical high signal (cytotoxic edema) Fluid attenuation inversion recovery image Subcortical high signal (vasogenic edema) Apparent diffusion coefficient map Cortical and subcortical low signal Perfusion magnetic resonance image Hyper-perfusion during ictal period Magnetic resonance angiography Prominent vasculatures, Increment of vascular diameter 3. 부종의뇌MRI 소견뇌부종을병리학적인관점에서보면혈관부종과세포독부종으로나누어볼수있다. 급성발작뇌병변으로발생한뇌부종에는병리학적으로다른이두가지부종을모두포함하고있다. 28 세포독부종은뇌신경세포가위치하는뇌겉질에주로발생하고, 혈관부종은주로겉질하부에발생한다 (Table 1, Fig. 1). 이부종중에세포독부종은확산강조영상에서잘관찰되고병변은고신호강도를나타낸다. 액체감쇠역전회복영상 (fluid attenuation inversion recovery image) 은혈관부종을잘보여주므로고신호강도가뇌겉질보다는겉질하부에강하게나타난다. 32 T1강조영상 (T1 weighted image) 에서는이러한부종들이저신호강도로나타난다 병변의시간적경과 1) 발작과병변의시간적인과관계뇌전증발작을유발시킨동물연구에서도발작에의해발생된뇌병변이시간이지나면서변하는것을확인할수있었다. 이런동물연구의결과는발작과급성발작뇌병변의인과관계를명확하게하는증거가된다. 33 발작과연관된급성병변이치료하고나서사라졌다가발작이재발하고나서다시발생했던증례들도보고되었다. 이러한증례들도다른원인이있는병변에의해발작이발생한것이아니라발작에의해급성병변이생겼다는인과관계를제시해준다. 13,27 미토콘드리아병과연관되어다초점뇌전증이있었던한명의환자에서특이한뇌병변들을관찰한보고도발작과병변사이의인과관계에대한증거를제시해주었다. 1 이환자의뇌에발생한병변은위치가변하는것이일련적으로촬영한뇌MRI에서관찰되었다. 그병변들은 T2강조영상과확산강조영상에서나타났으며, 이병변들은양자방출단층촬영 (positron emission tomography) 의소견과도일치하였다. 양자방출단층촬영에서는국소적으로대사가저하된부분들이관찰되었는데뇌MRI에서관찰되는병변과위치가 일치하였던것이다. 뇌파에서이상소견이최대인부위도병변과일치하였다. 이증례에서관찰된이동하는병변들도발작후에발생하고위치도기능적영상이나뇌파의이상소견과도일치하여, 뇌MRI에관찰되는소견이발작활성의결과이지원인이아니라는것에대해좀더확실한증거를제시해주었다. 2) 가역적특성급성발작뇌병변은대부분가역적이기때문에시간간격을두고뇌MRI를다시촬영해보면다른병변들과감별하는데크게도움이된다. 한번발생한급성발작뇌병변이유지되는기간은경우에따라다양하지만그병변들은대부분회복되어사라진다. 28 그러나수개월후에촬영한뇌MRI 영상에서도잔여병변이명확하게관찰되는경우도있다. 4,29 추적으로검사한뇌MRI 에서국소위축이발생하여 T2강조영상과확산강조영상에서신호의변화가발생하는것도간혹보고가된다. 그러나이러한보고들에서는환자가발작이발생하기전의영상과비교된자료가거의없어완벽한증거를제시하지는못한다. 2,3,13,14,31 5. T2투영효과 (T2 shine-through effect) T2투영효과는확산강조영상에서고신호강도로나타나기는하지만수분의확산이제한되어나타나는경우가아닌것을말한다. 이는 T2신호강도가증가된것이확산강조에투영되어나타나는소견이다. 겉보기확산계수지도는확산강조영상에서관찰되는고신호강도가 T2투영효과에의한것인지급성병변에의해발생한수분확산제한에의한것인지를감별하는데도움이된다. 급성발작뇌병변은수분의확산이줄어들기때문에겉보기확산계수지도에서신호의강도가떨어져나타난다. 겉보기확산계수지도를이용해도확산강조영상에나타나는병변의성격을제대로파악하지못하는경우도있다. LGI-1단백, NMDA수용체, GABA-B수용체들과연관되어발생하는변연계뇌염에의한뇌병변이그예이다. 이환자들에서는발작이반복 82

6 Oh-Young Kwon, et al. Brain lesions attributed to acute seizures 되고행동의변화가발생한다. 뇌MRI에서는변연계구조물에 T2신호의변화가생기고국소적위축이동반되지않으며조영증강이나타난다. 그러나겉보기확산계수지도에서는정상이거나 T2투영효과가나타나정상으로잘못판단할수도있다 영상에나타나는혈관과뇌관류의변화 1) 혈관의변화뇌MR혈관조영술 (brain magnetic resonance angiography) 을살펴보면발작이발생한부위의혈관이뚜렷해지거나직경이증가하기도하는데이것도급성발작뇌병변을급성뇌경색의병변과감별하는데도움이되는소견이다 (Table 1, Fig. 1). 혈관의직경이증가하지는않지만, 발작이발생했던대뇌반구에광범위하게병변이발생하였는데반해서혈관의변화가없는경우도관찰할수있다 (Fig. 2). 뇌전증지속상태환자에서뇌 MR혈관조영술을하면, 발작초점이되었던부위에혈관분지가뚜렷하게보였다가시간이경과하면서사라지는것을볼수있다. 이러한경과는혈류와관계되어조영이증가되는것을통해서도알수있다 (Table 1, Fig. 1, Fig. 2). 2,13,29 초기에급성발작뇌병변은혈액뇌장벽이허물어져조영증강이관찰되는데, 이조영증강은병변과그주변의연수막에관찰된다 (Table 1, Fig. 1, Fig. 2). 이조영증강소견은급성기에서는조영증강이관찰되지않는급성뇌경색에의한병변과구별이되는소견이기도하다. 28 발작이발생하는동안에정맥혈액이동맥화되는것도보고되었다. 유발되었거나자발적으로발생한뇌전증발작이있는동안뇌겉질을수술시야에서관찰한결과이다. 발작중에정맥혈액이동맥화하는것도급성발작병변에서혈관분지가시간에따라변화하는소견과일치한다. 13,35 따라서뇌MR혈관조영술에서관찰되는급성발작뇌병변에서뇌혈류가국소적으로증가하는것은동정맥션트 (arteriovenous shunting) 를의미할수도있다. 2) 뇌관류의변화발작이발생한뇌의부위에는뇌혈관이확장되고혈류가증가한다. 발작중에단일광자방출CT (single-photon emission CT) 를촬영하면급성발작뇌병변부위에뇌관류가증가한것을관찰할수있다. 급성발작발작환자에서뇌MRI 신호를연구한보고에서신호가증가한부위에뇌관류가증가한것을단일광자방출CT로확인하였다. 28 국소적으로뇌전증지속상태에있는환자에게 gadolinium으로조영증강을한민감도강조영상 (susceptibility-weighted imaging) 을촬영했을때발작부위에뇌관류가증가한것도보고되었다. 이환자에서단일광자방출 CT에서도같은부위에뇌관류가증가되었다. 36 발작의급성기에급성발작뇌병변에는관류가증가하기때문에급성기에관류가감소하는뇌졸중과다르다. 그러나이렇게관찰되는관류도시간이지나면서양상이달라진다는것을고려해야한다. 뇌관류MRI와단일광자방출CT는발작중에급성발작뇌병변에전형적이고국소적으로혈류가지나치게증가하는것을보여주지만과관류가나타나는부위의주위에는관류가저하되고발작이끝나고나서는같은부위에상대적인저관류가나타날수있다. 4,13,37-41 위에서소개한뇌전증지속상태에있던환자에서관찰된뇌관류의증가도시간이지나서는양상이달라졌다. 발작이멈춘후에는뇌관류MRI, 단일광자방출 CT 그리고뇌파에나타난이상소견이모두정상으로회복되었다. 36 발작이발생한후에급성발작뇌병변에관류저하가뇌관류MRI에나타나면급성뇌경색과감별이어려워진다. 3) 동맥스핀표지표준적인 MRI 기술이외에병태생리와연관된혈역학적변화를관찰하기좋고검사하기쉬운뇌관류MRI 영상이더해졌다. 동맥스핀표지기술 (arterial spin labeling) 이바로그영상이다. 뇌전증환자들에서동맥스핀표지를포함한뇌MRI와양자방출 CT를동시에검사를하면발작간저관류를관찰할수있었으며이소견은뇌파의이상소견이나양자방출CT에서관찰되는저관류와일치한다. 42 동맥스핀표지는자기적으로표지가된동맥혈에포함되어있고자유롭게확산하는성질이있는물양자를내인추적표지로이용하는검사이다. 이기법을사용할때에우선은두개의영상을만든다. 첫번째영상은흐름표지영상이다. 두번째영상은대조영상이다. 대조영상에서안정상태조직의신호는흐름표지영상과동일하지만, 영상단면에흘러들어오는혈액의자기화는다르다. 43 이기술에서는공간적으로선택된역전을이용한다. 44,45 촬영하려고하는조직으로동맥혈이유입되기전에무선주파수펄스를사용하여동맥혈에표지를한다. 조직으로흘러서들어가기전에동맥혈의물양자의방향을뒤집거나포화시키는것이다. 46 물양자가역전된혈액의 MRI신호는역전현상이없는다른조직에비해상대적으로음성이다. 표지가된혈액이조직에이르게되면, 영상에서조직의신호를약화시킨다. 표지가된영상을대조영상에서빼면표지가된양이영상에나타나고이것은조직에유입되는혈류의양을의미한다 (Fig. 3). 83

7 A B Figure 3. Hyperperfusion in a lesion attributed to serial GTC seizures in brain MRI from a 41-year-old man. Axial views of FLAIR images showing high signals in the anteromedial temporal area of the right hemisphere (A). ASL maps showing hyperperfusion at the same area (B). GTC: generalized tonic-clonic; MRI: magnetic resonance imaging; FLAIR: fluid attenuated inversion recovery images; ASL: arterial spin labeling. 다른관류영상에비해서, 동맥표지스핀기법은몇가지장점을가지고있으며, 현재에는많은의료기관에서일상적으로할수있는검사가되었다. 단일양전자CT, 조영증강CT 그리고 MR 관류영상은조영증강을위해서방사성추적자나조영제를환자에게투여해야하기때문에반복적로검사하기가어렵다. 이에반해서동맥스핀표지는환자에서조영증강을위해투여하는것이없다는점에서비침습적이다. 47,48 이와같이, 비침습적인방법으로조직의관류를측정할수가있어서동맥스핀표지는환자에서반복적으로검사를하여경과를관찰하거나병변의병태생리를연구하는데안성맞춤이다. 최근에는기술적발전으로인해민감도가증가하여더욱가능성을높였다. 가역뒤뇌병증후군이발생했었고발작이지속되었된 2명의환자에서동맥스핀표지를반복적으로검사한보고가있다. 49 이두명의환자에서반복적으로뇌MRI를촬영하여병변의시간적변화를관찰하였다. 동맥표지스핀과확산강조영상이뇌MRI검사에포 함되었고발작과연관하여일관성있는결과가관찰되었다. 발작이발생했을때에동맥표지핀에서는국소적으로관류가증가되었고, 확산강조영상에서는이부위에대뇌겉질의고신호강도가관찰되었다. 7. 동떨어진부위에서발생하는병변 1) 기능해리발생한병변과는거리가동떨어진뇌의구역에기능적손실이발생하는현상이기능해리이다. 기능해리가발생한부분은해부학적으로는동떨어져있지만신경세포의기능적측면에서는원발병변과연결되어있다. 교차소뇌기능해리는특히반대쪽대뇌반구의손상과연관이있다 (Fig. 4). 기능해리의병태생리는아직까지확실하지는않지만이러한기능적연결때문에발생하는것으로여겨진다. 발작활성에의해두구조사이에신 84

8 Oh-Young Kwon, et al. Brain lesions attributed to acute seizures A B C Figure 4. Cerebellar diaschisis attributed to acute seizures in a 51-year-old male with left frontal cortical dysplasia and agenesis of corpus callosum. Cytotoxic edemas were observed in the cortical areas of the left cerebral hemisphere and the contralateral cerebellar hemisphere in DWI (A) and ADC maps (B) of brain MRI. ASL maps also showed hyperperfusion in the same areas of the left cerebral hemisphere and the contralateral cerebellar hemisphere (C). DWI: diffusion-weighted images; ADC: apparent diffusion coefficient; MRI: magnetic resonance imaging; ASL: arterial spin labeling. 경회로의연결이늘어나고이들이흥분하여발생하는결과일것이다. 기능해리는뇌졸중에서가장흔하게기술되었으나, 다양한뇌의병리적상태에서발생할수있다. 편두통, 뇌종양, 뇌염등에서도기능해리가나타날수있는것이다. 50,51 MRI가보여주는기능해리의증거는수분확산제한과 T2신호증가이다. 이러한소견은전형적으로는시간이경과하면서회복된다. 그러나완전하게회복되지않고기능해리가나타난부분에만성손상이나용적감소와같은흔적이남을수있다. 기능해리에해당하는뇌MRI 소견이급성발작뇌병변으로나타나기도한다. 수분확산제한과 T2신호증가가급성발작활성이 85

9 A B C D Figure 5. A lesion of the corpus callosum splenium in a 19-year-old male. Brain MRI showing an isolated small lesion in the splenium of the corpus callosum on T2WI (A), FLAIR images (B), DWI (C), and ADC maps (D). T2WI: T2 weighted image; FLAIR: fluid-attenuated inversion recovery; DWI: diffusion-weighted image; ADC: apparent diffusion coefficient. 나타난반구와같은쪽의사이뇌와반대쪽의소뇌에관찰되는것이다. 이러한소견은뇌전증지속상태환자에서관찰된것이고발작이부분적으로발생한경우와전반적으로발생한경우모두에서관찰되었다. 2,4,13,24,25,29,30,52-54 발작이조절되고나서는이러한병변은대개수일이나수주가지나서사라진다. 일반적인기능해리의경우와마찬가지로급성발작과연관되어나타난기능해리가발생했던해부학적구조들에도위축이국소적으로발생하기도하였다. 25,30,51,53,54 2) 뇌량팽대병변뇌량팽대에발생하는일과성병변도뇌전증환자에서많이기술되었다 뇌MRI에서이러한병변은달걀과같은모양을하고있으며주변의경계가뚜렷하였다 (Fig. 5). 이병변은 T2신호가증가하였고뇌조직에수분의확산이제한되었고몇주가지난후에뇌MRI를촬영하면영상에서사라진다. 55,59 대부분의경우, 이러한병변은임상증상을유발하지않지만, 적은수의 환자에서정신이상이동반된경우들도보고되었다. 13 백질인뇌량팽대에병변이나타나는것외에는이러한병변들의기전은알려져있지않고정확한성격도알려져있지않다. 63 뇌량팽대에발생하는급성발작뇌병변의많은경우가수술전에비디오-뇌파감시장치를하기위해서항뇌전증약을급하게줄이는과정에서일련의발작이무리를지어발생한환자들에서기술되었다 ,59-61 이러한뇌량팽대에발생한병변은혈관부종이라고추정되었다. 57 그러나병변에서겉보기확산계수가감소된점은혈관부종이라는이론과는일치하지않고대신에그병변은발작활성그자체와연관이있다는것을시사한다. 55 뇌량팽대에발생하는급성발작뇌병변의병리학적소견은수초의극소공포형성 (micro-vacuolization) 이었다. 이병리학적소견이 T2신호증가와겉보기확산계수감소를설명하고뇌량팽대병변의가역성을설명해준다. 한보고에서는발작이없는상태에서뇌량팽대에병변이관찰되었다. 이보고의대상이 2명의환자는항뇌전증약의독성 86

10 Oh-Young Kwon, et al. Brain lesions attributed to acute seizures A B C D Figure 6. PRES in a brain magnetic resonance imaging from a 26-year-old woman with eclampsia. FLAIR images (A), DWI (B), and ADC maps (C) demonstrating vasogenic edema in the cortex and subcortical white matter of the parietal and occipital lobes. ASL imaging showing the increment of cerebral perfusion in the area (D). PRES: posterior reversible encephalopathy syndrome; FLAIR: fluid attenuation inversion-recovery; DWI: diffusion weighted images; ADC: apparent diffusion coefficient; ASL: arterial spin labeling. 과연관성이있었다. 그러나항뇌전증약과병변의연관성은증거가아직부족하다. 항뇌전증약을복용하는많은환자들이뇌MRI를촬영하였지만그러한병변이관찰되는일이드물기때문에항뇌전증약독성이있는상태에서뇌량팽대에병변이발생했던 2명의환자는예외적인것일수있다. 58 3) 가역뒤백질뇌병증백질의부종이대뇌의뒤쪽에광범위하게발생하고, 그병변은가역적이고좌우가대칭으로발생하는것이가역뒤백질뇌병증이다 (Fig. 6). 이증후군에서발작은임상양상의전형적인특징이다. 가역뒤백질뇌병증은대개고혈압뇌염, 자간, 세포독성약, 면역억제약등과연관되어발생한다. 64,65 그러나, 앞서언급한상황들이없이발작을한환자의영상에서가역뒤백질뇌병증가발생하는경우가있다. 이런경우에는발작자체가뇌 MRI 소견을발생시킨것으로판단할수밖에없으나실제의임상에서는모든상황을배제하기는힘들다. 갑작스러운혈압의 상승이가역뒤백질뇌병증의원인이되는데, 신체의혈압이환자의기저혈압에비해중등도로상승했을때에는이러한병변의원인으로생각하기는대개어렵다. 66 가역뒤백질뇌병증환자에서겉보기확산계수의수치가낮아지지않고오히려높아지는경우도있다. 이런경우에는급성발작뇌병변과는뇌MRI 소견이상충된다 감별진단의중요성급성발작뇌병변은다른병변과감별해낼수없는경우가많다. 발작과연관된급성병변은시간이경과하면서계속적으로변하기때문에영상검사를반복하여하면도움이되겠지만, 임상에서는치료방향을가능한빠르게결정해야하는경우가많다. 발작이발생한환자에서특징적인뇌병변이뇌MRI에서발견되었더라도환자에게발열이의식저하와같은증상들이있으면뇌염에의한가능성을고려하여치료를해야뇌염환자가적절한치료를받지못해악화되는것을막을수있다. 엄밀히 87

11 말하면이런질환의급성기에환자의뇌MRI에나타나는병변을단정하기는어렵다. 환자의뇌병변이뇌염에의한것일수도있고발작에의한것일수도있고두가지사항이복합적으로발생시킨병변일수도있다. 그러나임상적인사항을무시하고뇌MRI소견과발작에만집착을하면원인질환을간과하게된다. 이와는반대로, 급성발작뇌병변을급성기에비슷한양상을보이는뇌염, 뇌졸중, 뇌종양과같은질환들에의한병변으로잘못판단하면환자에게검사를과도하게하고적절하지않은치료를할가능성도있다. 2,14,67 뇌염외에급성뇌경색도뇌MRI소견을임상적으로꼭감별해야하는질환이다. 급성뇌경색에의해뇌MRI병변이발생하였다면치료가효과적이고위험이적은골든타임안에치료를하기위해서빠르게판단하는것이필요하다. 따라서급성뇌경색도뇌염처럼감별을뇌MRI 추적검사에의존할수가없다. 우선은 T2신호가증가되고뇌조직에서수분의확산이제한된소견을관찰해야한다. 비정상신호가나타나는구역이혈관의분포영역과일치하지않는경우는혈관성원인이라기보다는발작과관련이있는병변이라는단서가될수있다. 2 뇌MR혈관조영술에서혈관이뚜렷해지거나혈관의직경이증가하는것을관찰하거나, T1강조영상에서조영증강이증가하는것을관찰하면뇌경색을배제하는데도움을받을수있다. 뇌관류MRI나뇌관류CT를이용하여뇌관류를관찰하는것도도움이된다. 급성발작뇌병변에서는뇌관류가증가된다. 4,50,68 그러나시기에따라뇌관류가감소될수도있다. 뇌관류가감소되어있지만, MRI나 CT 관류영상에서평균통과시간 (mean transit time) 이양쪽대뇌반구사이에대칭을이루고있으면뇌경색이라기보다는발작후상태를의미한다. 68,69 결론 발작을하는도중이나발작이끝난직후에촬영한뇌MRI에서급성발작뇌병변을관찰할수있다. 병변이발작에의해서발생한것으로판단하기위해서는뇌병변을초래할수있는다른원인이없어야하지만두가지가동시에존재하는경우도있다. 급성발작뇌병변으로가장흔한것은국소부종이다. 뇌MRI로관찰하면 T2신호가증가하고, 뇌조직의수분의확산이제한되며, 조영증강이관찰된다. 추가적으로뇌MR혈관조영술, 뇌관류MRI가국소부종을다른병변과감별을하는데도움이된다. 경우에따라서는발작이발생하는부위와동떨어진곳에뇌병변이발생한다. 급성발작기에환자의뇌MRI에병변이나타났을 때, 임상가로어려운점은다른병변과구별을하기어려우며환자를적절하게치료를하기위해빠르게판단해야하는경우가많다는것이다. 급성발작뇌병변은가역적인경우가많아서대부분사라지지만, 병변이남는경우도있고병변이사라지는시기도다양하다. 그러나임상적으로판단한적절한시기에뇌 MRI를추적하여검사하면확진하는데도움이된다. REFERENCES 1. Cole AJ. Status epilepticus and periictal imaging. Epilepsia 2004;45: Lansberg MG, O Brien MW, Norbash AM, Moseley ME, Morrell M, Albers GW. MRI abnormalities associated with partial status epilepticus. Neurology 1999;52: Briellmann RS, Wellard RM, Jackson GD. Seizure-associated abnormalities in epilepsy: evidence from MR imaging. Epilepsia 2005;46: Szabo K, Poepel A, Pohlmann-Eden B, Hirsch J, Back T, Sedlaczek O, et al. Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. Brain 2005;128: Wieshmann UC, Symms MR, Shorvon SD. Diffusion changes in status epilepticus. Lancet 1997;350: Ebisu T, Rooney WD, Graham SH, Mancuso A, Weiner MW, Maudsley AA. MR spectroscopic imaging and diffusionweighted MRI for early detection of kainate-induced status epilepticus in the rat. Magn Reson Med 1996;36: Petroff OA, Prichard JW, Ogino T, Avison M, Alger JR, Shulman RG. Combined 1H and 31P nuclear magnetic resonance spectroscopic studies of bicuculline-induced seizures in vivo. Ann Neurol 1986;20: Petroff OA, Prichard JW, Behar KL, Alger JR, Shulman RG. In vivo phosphorus nuclear magnetic resonance spectroscopy in status epilepticus. Ann Neurol 1984;16: Young RS, Osbakken MD, Briggs RW, Yagel SK, Rice DW, Goldberg S. 31P NMR study of cerebral metabolism during prolonged seizures in the neonatal dog. Ann Neurol 1985;18: Najm IM, Wang Y, Shedid D, Lüders HO, Ng TC, Comair YG. MRS metabolic markers of seizures and seizure-induced neuronal damage. Epilepsia 1998;39: Najm IM, Wang Y, Hong SC, Luders HO, Ng TC, Comair YG. Temporal changes in proton MRS metabolites after kainic 88

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