KISEP Original rticle 대한간질학회지 2006;10(2):111-117 경련후뇌자기공명영상소견의역동적변화양상 강희진 1 김지현 1 이정화 1 김희진 1 송현석 1 최경규 1 박기덕 1 임수미 2 이향운 1 이화여자대학교의과대학신경과학교실의과학연구소, 1 방사선과학교실 2 Dynamic Changes of MRI Findings after Seizures Hee Jin Kang, M.D. 1, Jee Hyun Kim, M.D., Ph.D. 1, Jung Hwa Lee, M.D. 1, Hee Jin Kim, M.D. 1, Hyun Seok Song, M.D. 1, Kyoung-Kyu Choi, M.D., Ph.D. 1, Kee-Duk Park, M.D., Ph.D. 1, Soo Mee Lim, M.D., Ph.D. 2 and Hyang Woon Lee, M.D., Ph.D. 1 Department of Neurology 1 and Radiology, 2 Ewha Medical Center, College of Medicine, Ewha Womans University and Ewha Medical Research Institute, Seoul, Korea Introduction: Magnetic resonance imaging has demonstrated reversible peri-ictal MRI changes suggestive of hemodynamic changes or cytotoxic edema. We were to investigate the dynamic peri-ictal MRI changes in patients with seizures. Methods: We retrospectively reviewed the medical records, electroencephalography, and initial and follow-up MRI of 5 patients with single seizure or status epilepticus. We analyzed the patterns and locations of MRI abnormalities and their relationship with characteristics of seizures. Results: Two patients with complex partial seizures (CPS) and versive or unilateral tonic seizures showed high signal changes in frontal cortex on T2-weighted (T2WI), fluid attenuated inversion recovery (FLIR) and DWI. Three patients had MRI changes in mesial temporal structures including hippocampus after single generalized tonic-clinic seizure without encephalitic features clinically. One patient had multiple signal abnormalities in the left temporo-parietal, mesial temporal, insular cortices and thalamus on T2WI and FLIR after frequent CPS. ll of the lesions disappeared or resolved partially on the follow-up MRI. Conclusion: Our results showed that variable MRI changes in peri-ictal phase are possible at cortical as well as at subcortical areas. The dynamic MRI changes can be associated even in patients with single clinical seizure, suggesting that these changes are not related to the seizure frequency. (J Korean Epilep Soc 2006;10(2):111-117) KEY WORDS: Peri-ictal MRI Dynamic Seizures. 서 론 대부분의경련은수분정도지속되며, 한두차례의경련으로인해만성적인또는비가역적인뇌조직의변화를보이지는않는다. 간혹경련후 Todd paralysis 라고하는일시적인운동마비증상이있는데, 통상하루를넘지는않는다. 1 그밖에도경련후의일시적인현상으로감각마비, 의식변화, 언어마비등이보이는경우가있어 Todd phenomena 라고한다. 오히려환자들이경련후에지속적인 Received 20 November 2006 ccepted 27 December 2006 Corresponding author: Hyang Woon Lee, M.D., Ph.D., Department of Neurology, College of Medicine, Ewha Womans University, 911-1 Mok-dong, Yangcheon-gu, Seoul 158-710, Korea E-Mail: leeh@ewha.ac.kr 신경학적이상이있다면경련외에뇌졸중이나뇌출혈, 뇌종양, 뇌염과같은다른원인을반드시감별할필요가있다. 뇌자기공명영상 ( 이하 MRI) 은간질환자를진단하고그원인을밝히는데있어필수적인검사이다. 대개처음경련이발생한환자의경우경련의원인이될만한뇌병변이있는지뇌영상, 특히 MRI 가필요하지만, 원인을알고있는경우나최근에 MRI 를시행한경우등모든경련후에뇌영상이필수적이지는않다. 1980 년에 Rumack 등이간질환자의뇌컴퓨터단층활영에서가역적인뇌영상변화를처음보고한이후, 2 최근에는 MRI 상에서도가역적인뇌병변을보이는경우가보고되고있다. 3-6 국내에서도간질환자에서의이러한가역적뇌영상변화에대한증례가이미보고된바있는데, 이러한소견에대한인지는경련전후의병태생리적변화를이해할수있게하고일부에서는향후불필요한추가검사나치료를피할수도있어임상적으 대한간질학회지 2006;10(2):111-117 111
Dynamic Changes of MRI after Seizures 로중요한의미가있다. 7 본연구에서는경련후 MRI를시행하여일시적인뇌영상의변화를보였던 5명의환자증례를통해경련발작전후에관찰할수있는 MRI의특징적변화와병변의위치를파악하여다른질환과어떻게감별해야할것인지를살펴보고자한다. 또한본연구는이러한병변이간질발작의종류와빈도, 혹은동반된내과적상태나환자의신경학적상태와어떠한연관성이있는지에대해논의하고자한다. 대상과방법 본연구는처음발생하거나재발한경련발작으로입원하여 MRI 를시행받은환자중에뇌경색이나뇌출혈, 뇌종양, 뇌염등과같은뚜렷한뇌병변없이 MRI 에서비특이적이고광범위한신호강도이상을보였다가추적 MRI 상병변이사라진 5명의환자들을대상으로하였다. 환자는모두남자였으며나이는 51세에서 76세로평균연령은 69.3 세였다. 환자들은모두응급실로내원하였고경련은부분또는전신경련양상으로 5분에서 12시간까지지속되었다. 4명의환자는모두첫번째경련발작이었고나머지 한명은 10여년전부터간질진단하에항경련제를복용해온기왕력이있었다. 경련발생후첫번째 MRI 검사는 4명의환자에서는 24시간이내에, 그리고 1명의환자는 4 일후에시행되었다. 두번째 MRI 는짧게는 2주후부터길게는 1년후에 1차례혹은 2차례재시행하였다. MRI 는경련의원인이될수있는뇌경색, 뇌출혈, 뇌종양혹은뇌염등의여부를확인하기위해시행하였는데, 5명모두 T2 강조영상 (T2-weighted image, T2WI), 액체감약반전회복 (fluid-attenuated inversion recovery, FLIR) 과조영제강화 (contrast enhancement) 영상을포함하였고, 그중 4명에서확산강조영상 (diffusion-weighted image, DWI) 과겉보기확산계수 (apparent diffusion coefficient, DC) 가시행되었다. 아울러환자들의증상및임상경과, 뇌파및 MRI 소견을후향적으로검토하였다. 결과 대상환자들의나이와동반질환, 나타나는뇌파소견, MRI 시행시기및영상소견은 Table 1에정리하였다. 환자 1은만성알코올사용자로내원당일왼쪽팔에체성감각성전구증상과함께양눈의좌측으로의공동편위를동 Table 1. Clinical profiles of the patients Patient Sex/ age Combined Seizure and EEG findings Timing of MRI conditions Type Frequency EEG Initial Follow-up 1 M/76 lcohol dependence CPS with Lt version Several times IS, Rt 4 days 1 & 6 mon 2 M/71 Hyperglycemia CPS with Lt version >10 times EEG seizure, Rt F 1 days 10 days 3 M/60 Negative CSF study apparently GTC Once SW & CS, Lt F-T 1 days 1 year 4 M/51 Hypoglycemia Rt versive, tonic & Continous (>24 hrs) SW & CS, Lt F 1 days 2 wks status epilepticus 5 M/71 DM Complex partial status epilepticus Continous (<12 hrs) PLEDs, Lt hemi 1 days 2 & 4 wks M, male; DM, diabetes mellitus; CPS, complex partial seizure; GTC, generalized tonic-clonic; hrs, hours; IS, intermittent slow; Rt, right; F, frontal; SW, sharp waves; CS, continuous slow; F-T, frontotemporal; PLEDs, periodic lateralized epileptiform discharges; Lt, left; hemi, hemisphere; mon, months; wks, weeks Table 2. Initial peri-ictal and follow-up MRI findings Initial signal abnormality Follow-up study Patient DWI/DC/ DWI/DC/ Location T2/FLIR T2/FLIR Location 1 / / / Rt hippocampus / / / Nearly disappeared / /N/N Disappeared 2 / / / oth frontal cortex / / / Partially resolved 3 N/N/ / Rt hippocampus & uncus N/N/ / Rt hippocampal atrophy without signal change 4 / / / Lt frontoparietal cortex / /N/N Nearly disappeared 5 / / / Lt mesial temporal, occipital, frontoparietal, / /N/N Partially resolved thalamus & insular areas N/N/ / Disappeared except Lt hippocampus & F pole N, not performed;, high signal intensity;, high signal intensity;, no definite signal change;, both high and low mixed signal intensity; Rt, right; Lt, left; F, frontal 112 대한간질학회지 2006;10(2):111-117
강희진 김지현 이정화등 C D Figure 1. MRI and EEG findings in patient 1. Initial MRI shows increased signal intensity in diffusion-weighted (white circle) () and decreased signal in DC map (white circle) (). Follow-up MRI obtained one month later shows nearly complete resolution of the hippocampal signal changes in diffusion-weighted (C) and DC (D) images. Figure 2. MRI and EEG findings in patient 2. : Initial diffusion-weighted MR images reveal increased signal intensity mainly in the right frontal and partly in the left medial frontal cortical areas (upper row). Follow-up diffusion-weighted images obtained 10 days later show the resolution of the signal changes in the same cortical area (lower row). : EEG seizure starts from the right frontal region. 반한복합부분발작이수차례반복되어내원하였고이러한증상은 1시간이내에회복되었다. 신경학적검사상미약한좌측편마비가관찰되었으나수시간후회복되었고, 이학적검사상열은없었다. 혈액검사상암모니아가상승 (90~100 μg/dl) 해있었으나뇌척수액검사상에서이상소견은없었으며, 뇌파에서는우측반구에서간헐적서파가관찰되었으나간질파는없었다. 환자 2는 10년전당뇨와간질을진단받고꾸준히투약중이던환자로역시좌측으로의편위를동반한복합부분간질양상을 10여차례보여내원하였다. 내원시혈청에서항경련제 ( 페니토인 ) 농도는치료용량보다약간낮은상태였고혈당은 556 mg/dl 으로높은상태였다. 내원시혼수상태였던의식은항경련제투여후바로다음날정상적으로회복되었다. 내원당일시행했던뇌파검사상우측이마엽에서뇌파상경련이있었으나 1주일후에는같은부위에간헐적서파만관찰되었다 (Figure 2). 환자 3은내원약 4년전부터좌측편마 비가있던상태로거동이약간불편한상태였으나이에대해특별한검사나치료를받은적은없었다. 환자는내원당일의식잃고쓰러진채발견되었고타병원에서외견상전신근간대성경련을보였다. 뇌척수액검사상이상소견은관찰되지않았고뇌파검사상우측관자엽 (temporal lobe) 에서극파와간헐적서파가관찰되었고내원당일 24 시간내에의식은바로회복되었다 (Figure 3). 환자 4 는만성알코올사용자로좌측기저핵부위의뇌출혈, 알코올성말초신경병증으로진단받은병력이있는분으로내원당일의식소실과함께머리와눈이우측으로돌아가면서우측팔다리가뻣뻣해지다가간질중첩증으로이어지는경련양상을보였는데이런증상은 24시간이상지속되었다. 내원시우측의미약한편마비가관찰되었고내원시혈당은 32 mg/dl 로저혈당상태였으며, 암모니아가 88 μg/dl 로다소상승된소견을보였다. 뇌파검사상좌측이마엽 (frontal lobe) 에예파와지속적서파가관찰되었다 대한간질학회지 2006;10(2):111-117 113
Dynamic Changes of MRI after Seizures Spike, F8 Figure 3. MRI and EEG findings in patient 3. : Initial FLIR and T2-weighted MR images reveal increased signal intensity in the right hippocampus indicated by white circles (upper row). Follow-up FLIR and T2-weighted images obtained one year later show the right hippocampal atrophy with resolution of the signal changes in the same area indicated by white circle (lower row). : EEG shows sharp waves and continuous slow in the right anterior temporal region. Figure 4. MRI and EEG findings in patient 4. : Initial diffusion-weighted MR images reveal increased signal intensity in the left frontoparietal cortical and part of the subcortical white matter indicated by white circles (upper row). Follow-up diffusion-weighted images obtained 2 weeks later show complete resolution of the signal changes in the same area (lower row). : EEG shows left frontal sharp waves and continuous slow of the left frontotemporoparietal areas. 가 4일후에는정상화되었다 (Figure 4). 환자 5는당뇨와고혈압으로투약중이던환자로우측으로의동향주시와우측에서 Todd paralysis 를보이는복합부분간질중첩증 (complex partial status epilepticus) 상태가지속되다가항경련제사용후 12시간만에호전되었다. 내원시혈액검사상에서특이소견은관찰되지않았으나뇌파상에서는좌측반구에서 periodic lateralized epileptiform discharges (PLEDs) 가관찰되었다 (Figure 5). 환자들에게시행한일차및추적 MRI 소견은 Table 2 에정리하였다. 일차시행한 MRI 에서유사한경련양상을보였던환자 1과 2는그병변부위가각각우측해마 (hippocampus) 와양측이마엽 (frontal lobe) 피질부위에서확인되었다. 환자 1은 DWI, T2WI 및 FLIR image 상우측해마에서고신호강도, DC map 에서는저신호강도가관찰되었고같은부위에조영증강이관찰되었다 (Figure 1, ). 따라서이환자의경우초기에는우측해마경색이의심되었으나, 환자의신경학적소견이경련후일시적인 Todd paralysis가있다가완전히회복되었으며 1개월과 114 대한간질학회지 2006;10(2):111-117
강희진 김지현 이정화등 Figure 5. MRI and EEG findings in patient 5. : Initial diffusion-weighted MR images reveal increased signal intensity in the mesial and lateral temporal (upper left, white circle), thalamus, insular (upper second left), frontal and parietal cortical areas (upper third and right). Initial DC map shows signal changes in the same area with increased signal intensity in the left mesial temporal (middle left, black arrow within white circle) and decreased intensity in the temporal gray and white matters (middle left, white arrow in white circle). Follow-up MRI obtained 4 weeks later shows the left hippocampal atrophy and residual signal change (lower row). : EEG reveals periodic lateralized epileptiform discharges (PLEDs) in the left hemisphere. 6개월후각각 MRI 를재시행하였을때이병변은모든영상에서사라져경련과관련된변화로판단되었다 (Figure 1C, D). 환자 2의경우 FLIR 상우측이마엽앞부분과일부좌측내이마엽 (medial frontal) 대뇌피질부위에고신호강도가관찰되었으며 10일후재검사시에는이러한변화는거의관찰되지않았다 (Figure 2). 전신성강직근간대성발작 (generalized tonic-clinic seizure, 이하 GTC) 을보였던환자 3에서는환자 1에서와유사하게우측해마를포함한내측관자엽 (mesial temporal lobe) 에서 FLIR 와 T2WI 에서고신호강도를보였고조영증강 (gadolinium enhancement) 소견이관찰되어있었다. 1년후재검사시신호강도에서의변화는현저히호전되고조영증강소견도사라졌으며해마위축 (hippocampal atrophy) 이관찰되었다 (Figure 3). 간질중첩증 (status epilepticus) 의상태로내원하였던환자 4와 5는 MRI 변화의위치나양상이전혀다른소견을보였다. 우측으로머리와눈의편위가있고우측팔다리의강직성경련을보이는부분발작이지속되고좌측이마엽간질파 (epileptiform discharges) 가관찰되었던환자 4에서는환자 1과같이좌측이마엽과마루엽피질 (parietal cortex) 에국한된고강도신호가관찰되었으나조영증강소견은없었다 (Figure 4). 반면, 환자 5의경우좌측해마를비롯한내측관자엽, 마루엽, 이마엽경계부위와전두극 (frontal pole) 의광범위한부위와일부시상 (thalamus), 뒤통수엽 (occipital lobe) 경계 부위와섬이랑 (insuar) 근처의대뇌피질에서신호강도가증가된소견을보였다 (Figure 5). 환자 5의경우특히고혈압, 당뇨, 고령이라는위험인자가있고갑자기발생한우측편마비로인해임상적으로는뇌졸중과의감별이필수적이었고, 조영증강소견은뚜렷하지하지않으면서 DWI 상신호강도의상승과 DC map 상저하가관찰되었다. 그러나일부백질부위에는오히려 DC가증가된부분이함께있었고뇌혈관의전순환 (anterior circulation) 과후순환 (posterior circulation) 의병변이혼재되어있을뿐아니라혈관영역으로잘설명되지않았다. 2주후 MRI 를다시시행한결과이러한일련의변화들은현저히호전되었고, 4주후에재시행한 MRI에서는좌측해마를제외한대부분의병변이사라져뇌졸중으로인한병변일가능성은적은것으로판단되었다. 고찰 본연구는서로다른원인으로인해유발된경련을주소로내원했던 5명의환자들을대상으로경련후에보이는 MRI 소견의역동적인변화양상을기술하였다. DWI 상에서보였던고신호강도는대부분가역적이었으며 DC 의변화는초기에저신호강도를보이다가고신호강도로전환되는경우도있고일부에서는신호증가와감소소견이혼재해있었으며, T2WI 와 FLIR 상의신호증가소견과 대한간질학회지 2006;10(2):111-117 115
Dynamic Changes of MRI after Seizures 동반되어있었다. 이러한 MRI 소견은대부분가역적이었으나일부신호변화가잔존하거나신호변화는소실되었으나추적 MRI 상병변부위의뇌위축이동반되는경우가있었다. 그러나, 4명의환자에서는고혈당, 알코올의존성, 고암모니아혈증이동반되어 MRI 소견에영향을주었을가능성을완전히배제하기는어려웠다. 이러한가역적뇌병변의기전은아직확실하게알려지지는않았으나과관류 (hyperperfusion), 혈관성 (vasogenic) 또는세포독성부종 (cytotoxic edema) 로설명하려는주장이우세하다. 3,14 즉, 간질발작이있을때발작부위및그와관련된뇌피질부위에대사율과산소소비가증가되지만호흡량이줄어들게되면혈중산소분압이감소하고이산화탄소분압이증가하게되어뇌젖산을증가시킴으로써뇌혈관의확장과정상적인산소농도를위한뇌혈류량의증가가나타나게된다는것이다. 3 발작후혈류증가의기간은일반적으로 30분이내에정상으로회복되는것으로알려져있으나지속적인발작후또는발작간관류증가가보고된적도있다. 9 경련의지속기간과 MRI 병변의가역성과의상관관계에대해서는논란이있는데, 일부연구에서경련후뇌영상의변화가발작의빈도와기간에비례한다는보고가있었으나, 10,15 다른연구에서는발작의빈도와무관하게단한번의발작후에도 MRI 변화가나타났던보고도있었다. 7,11 본연구에서환자들의경련지속기간과뇌병변의정도사이에연관성은관찰되지않았다. 경련후뇌영상의변화소견은주로해마나대뇌피질일부뇌량에서도보고된바있고, 대뇌피질의경우간질파가발생한부위에서대개영상이상이관찰될것으로생각되며마루엽이나관자엽의피질부위에주된이상을보이는경우가많았으나이마엽이나뒤통수엽에서보고된경우도있다. 8,10 본연구에서기술한환자들에서도해마또는대뇌피질에서주로이상소견을보였으며, 대개뇌파상간질파가관찰된부위근처이거나최소한동측에서관찰된경우가대부분이었다. 환자 2의경우뇌파상간질파가관찰된우측이마엽대뇌피질에서가장현저한영상강도가증가된변화를보였으나일부좌측내이마엽피질부위에서도영상증강소견이동반되었고, 환자 4에서는간질파가관찰되었던좌측전두엽부위피질뿐만아니라시상등피질하부위에서도이상소견을보였다. 또한경련후초기에나타난신경학적증상이대부분 MRI 상에서의병변부위와연관성을보이고있었다. 지금까지언급했던경련후 MRI 에서가역적이상소견은대체로 DWI, FLIR, T2WI 에서고신호강도를주로보 이고특히 DWI 는세포독성혹은혈관부종을보다빨리감지할수있는것으로알려져있다. 6 한편부분간질중첩증의경우간질발생지점 (epileptogenic foci) 의경우 DC 값의저하가관찰되는데대개전신근간대성경련이나간질지속증후 6~28% 에서 3일이내에관찰되는것으로보고되고있다. 4 이러한 DC 값의저하는피질신경세포내에서나트륨농도상승이나흥분성아미노산의과다방출에의한세포독성부종과관련되어있고, 3,6,12,16,17 이런병태생리적변화들은해마경화증이나다른해마발달이상의기전적근거가된다. 18,19 그러나내관자엽간질 (mesial temporal lobe epilepsy) 과비병변성신피질간질 (nonlesional neocortical epilepsy) 의경우 DC 값이지속적으로상승혹은저하된경우도있으며때로는복잡하고다양한양상의변화들이동시에관찰되기도하였다. 이러한소견들은 MRI 시행시기나경련의지속기간들과상당히밀접한관계가있을것으로추정된다. 20 일부선행연구에서 DC 값의상승은대뇌피질의 DC 저하와함께백질부위의 DC 상승이동반되거나, 간질지속증과같이경련기간이연장될때, 일부에서는 1~18 개월이상경과한후부분적인뇌위축이나뇌손상이일부남게되는경우 CD 의상승을유발할수있다고하며, 혈관- 뇌장벽의손상으로인한혈관부종으로설명하려는시도가있었다. 6,13 실제로 MRI 특히 DWI 상조영증강이관찰된부위에서 SP- ECT상뇌혈류증가가동반된예들도보고되고있다. 7,16 이러한 DWI 에서의고신호강도와 DC 값의상승혹은저하는다른질환과의감별에있어반드시고려해야하는데, 급성뇌경색, 정맥혈전증, 종양, 안근마비성편두통, 대사성뇌병변및일부뇌염에서도같은양상의변화를관찰할수있다. 10,21-28 특히간질후관찰되는뇌영상의변화가반드시특정한양상으로나타나지않고환자마다매우다양한양상으로나타나기때문에 DC map 과 DWI 에서신호강도변화여부만으로는다른질환과의감별이어려울수있다. 따라서감별진단을위해서는임상증상이나징후는물론이고여러영상들의신호강도변화와혈관영역등에대한복합적인고려가필요하고아울러필요할경우 MRI의재시행이나뇌혈류검사, 뇌척수액검사및뇌파등추가적인검사도지연되어서는안될것이다. REFERENCES 1. Wyllie E. The treatment of epilepsy. 4th ed. Philadelphia: Williams and Wilkins, 2006;225-8. 2. Rumack CM, Guggenheim M, Fasules JW, urdick D. Transient positive postictal computed tomographic scan. J Pediatr 1980;263-4. 3. Lansberg MG, O rien MW, Norbash M, Moseley ME, Morrell M, lbers GW. MRI abnormalities associated with partial status epil- 116 대한간질학회지 2006;10(2):111-117
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