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1 원저 두개내동맥경화증이뇌경색이후의장기사망률에미치는영향 을지대학교의과대학을지병원신경과, 고려대학교의과대학의학통계학과 a, 분당서울대학병원신경과 b 강지훈장윤숙이준영 a 김병건구자성권오현박종무이정주배희준 b Impact of Intracranial Cerebral Atherosclerosis on the Long-term Mortality after Ischemic Stroke Jihoon Kang, M.D., Yoonsook Jhang, M.D., Juneyoung Lee a, Byung-kun Kim, M.D., Ja-Seong Koo, M.D., Ohyun Kwon, M.D., Jong-Moo Park, M.D., JungJu Lee, M.D., Hee-Joon Bae, M.D. b Department of neurology, Eulji General Hospital, Eulji University College of Medicine, Department of Biostatistics, School of Medicine, Korea University a, Department of neurology, Seoul National University Bundang Hospital b Background: Intracranial cerebral atherosclerosis (ICAS) is an important cause of stroke, but it is not well-known whether and how much it contributes to the long-term prognosis of stroke patients. The purpose of this study was to elucidate the impact of ICAS on the long-term mortality of patients with acute ischemic stroke. Methods: From November 1998 to December 2002, a consecutive series of 1306 patients who were hospitalized due to acute ischemic stroke were listed in the stroke registry. Among them, 946 patients who underwent brain MRI and MRA were selected and their vital status was identified by the National Death certificates. Results: Among 946 subjects, 624 (65.9%) had ICAS, while 106 (11.2%) had extracranial carotid atherosclerosis (ECAS). During a period of 59 months (27±16 months), 220 patients died. The 30-day, 1-year, 2-year, 3-year, and 4-year mortalities were 2.8%, 14.5%, 22.9%, 27.8% and 35.1% for those with ICAS (N=624); whereas 2.2%, 7.7%, 13.2%, 15.4% and 19.2% for those without ICAS (N=322) (p= on log rank test). Crude hazard ratio (HR) of ICAS was 1.9 (95% confidence interval, 1.39 to 2.62), but adjusted HR of ICAS was 1.16 (0.82 to 1.62). The number of intracranial arteries with atherosclerosis and the existence of symptomatic ICAS were also considered. Both of them were significant predictors of the long-term mortality in crude analyses, but lost their significance after adjustments. Conclusions: This study failed to prove the independent contribution of ICAS to the mortality of patients with acute ischemic stroke. J Korean Neurol Assoc 25(4): , 2007 Key Words: Intracranial atherosclerosis, Symptomatic, Long-term, Mortality, Acute ischemic stroke 서론 Received April 6, 2007 Accepted June 5, 2007 *Hee-Joon Bae, M.D. Department of Neurology, Seoul National University Bundang Hospital, 300, Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, , Korea Tel: Fax: braindoc@snu.ac.kr * 본연구는보건복지부보건의료기술진흥사업의지원에의하여이루어진것임 (A B N A). 백인에서흔하게보이는근위경동맥의동맥경화증이장기예후에미치는영향에대해서는비교적잘알려져있으며증상발현유무와협착정도에따라혈관성형술등의적극적인치료를시행하고있다. 1-3 이에비해동양인, 흑인과라틴아메리카인의경우두개내동맥경화증에의한뇌경색이많은것으로보이나 4-8 장기예후에 462

2 두개내동맥경화증이뇌경색이후의장기사망률에미치는영향 대한보고는거의없었다. 9,10 최근뇌경색환자를대상으로경두개도플러초음파검사를이용해두개내동맥경화를진단하여이들의장기예후를조사한연구가있었으나 11,12 경두개도플러초음파의단점을제기할수있고, 두개내동맥경화증의협착정도, 침범된혈관개수, 증상발현유무등의특징이예후에미치는영향에대해서는밝히지못했다. 본연구에서는뇌자기공명혈관조영술을시행한급성기뇌경색환자들을대상으로두개내동맥경화증이이들의장기예후에미치는영향을두개내동맥경화증의유무, 정도및증상의발현여부의측면에서조사하고자하였다. 대상과방법 본연구는을지뇌졸중등록체계 (Eulji Stroke Registry) 를이용한후향적연구로 1998 년 11월부터 2002 년 12월까지뇌졸중으로을지병원신경과에입원하여등록된 1306 명중, 급성뇌경색으로증상발생일주일이내에내원하여뇌자기공명혈관조영술을시행한 946 명을대상으로하였다. 출혈성뇌졸중이나각종진단검사에서뇌경색이아닌질병으로판명된환자및뇌자기공명혈관조영술을시행하지않은환자는제외하였다. 장기예후의지표로는사망을이용하였으며 1998 년부터 2003 년까지통계청에서발표하는사망원시자료를사용하여사망여부와사망일시, 사망원인을확인하였으며사망하지않은경우에관찰종료시점은 2003 년 12월 31일로하였다. 환자의나이, 성별, 흡연력, 음주력등의인구사회학적요인, 뇌졸중기왕력, 허혈성심장질환, 심방세동등의심장질환력, 당뇨, 고혈압, 고지혈증유무등의병력, 내원시 NIHSS (National Institute Health stroke scale) 점수, TOAST 분류법에의한뇌경색아형, 13,14 치료방법과퇴원시 MRDS (Modified Rankin Disability Scale) 점수등에대한자료는뇌졸중등록체계를활용하여수집하였다. 뇌자기공명촬영은 GE사의 1.5 Tesla 자기공명영상을이용하였으며혈관촬영은 2D-TOF (time of flight) 법으로영상을얻었다. 뇌자기공명혈관조영술로촬영한뇌혈관은두개외혈관과두개내혈관으로나누었으며두개외동맥경화 (ECAS, Extracranial atherosclerosis) 는두개외내경동맥 (extracranial internal carotid artery) 의동맥경화를, 두개내동맥경화 (ICAS; Intracranial atherosclerosis) 는두개내내경동맥 (Intracranial internal carotid artery), 중대뇌동맥 (Middle cerebral artery) 의 M1분절, 전대뇌동맥 (Anterior cerebral artery) 의 A2분절, 후대뇌동맥 (Posterior cerebral artery) 의 P1분절, 뇌저동맥 (Basilar artery) 과두개내척추동맥 (Intracranial vertebral artery) 의동맥경화로정의하였다. 동맥경화율은한명의신경과의사가측정하였으며 WASID (Comparison of wafarin and aspirin for symptomatic intracranial arterial stenosis) 연구에서혈관조영술로동맥경화율을측정할때시행한방법을동일하게적용하였다. 15 뇌자기공명혈관조영술에서동맥경화가있는동맥의원위정상부위를 N, 동맥경화부위를 D라고하였을때동맥경화율 = (1-D/N) 100(%) 으로하였으며동맥경화증의정도에따라경도 ( 동맥경화율 <50%), 중등도 ( 동맥경화율 >50%), 고도 ( 국소적인조영음영결손 ), 폐색 ( 협착이후조영음영결손 ) 의 4개의등급으로나누었다. 이중동맥경화율이중등도이상인경우를의미있는협착으로생각하였으며중등도이상의동맥경화가있고해당혈관영역에부합되는뇌경색이관찰될때증상성동맥경화로하였으며일과성뇌허혈의경우환자의증상이확실히해당동맥경화로부터기인하였다고생각되는경우에만증상성동맥경화라고하였다. 무증상성동맥경화는중등도이상의동맥경화가있으나뇌경색이발생하지않은경우를말하였다. 통계분석은우선카플란마이어방법 (Kaplan-Meier survival analysis) 으로급성뇌경색의사망률을조사한다음, 두개내동맥경화의특성과사망률의관계를로그랭크검사 (Log rank test) 로분석하였다. 먼저두개내동맥경화와두개외동맥경화의유무에따라사망률이다르게나타나는지알아보았다. 둘째, 두개내동맥경화의정도와사망률의관계를알아보기위해서두개내동맥경화의수를기준으로하여, 그숫자가한개, 두개그리고세개이상인군으로나누어이들의사망률차이를알아보았다. 셋째, 두개내동맥경화의위치가전방순환과후방순환에따라서사망률이다르게나타나는지알아보았으며, 마지막으로증상성두개내동맥경화와무증상성두개내동맥경화의사망률을비교해증상유무에따라사망률이다른지알아보았다. 다음콕스회귀분석 (Cox regression analysis) 을이용하여두개내동맥경화의유무, 정도, 증상유무각각에대해 crude hazard ratio (HR) 및 adjusted HR 을구하였다. 다변량분석에사용된교란변수는동맥경화이외에환자들의요인들중카플란마이어분석후로그랭크분석에서 p-값이 0.2 이하인변수를선택하였다. 통계프로그램으로는 SPSS (version 13.0) 를사용하였으며 p값이 0.05 미만일때를통계학적으로의미가있는것으로해석하였다. 결과 연구에포함된환자 946 명의평균나이는 64.7±11.6 세이고 65세이상환자가 53.8% 이었으며관찰기간은평균 27±16개 J Korean Neurol Assoc Volume 25 No. 4,

3 강지훈장윤숙이준영김병건구자성권오현박종무이정주배희준 월, 최장관찰기간은 59개월이었다. 남성이 467 명 (49.4%) 이었으며고혈압 63.2%, 당뇨 43.4%, 고지혈증 19.3% 으로조사되었으며, 허혈성심질환 9.8%, 심방세동 9.2%, 그리고이들을포함해심인성색전원인을갖는사람은 13.7% 에서관찰되었고흡연력 31.5%, 음주력 30.7% 이었다. 뇌졸중기왕력은 31.9% 이었는데이중출혈성뇌졸중 4.2%, 뇌경색 27.7% 이었다. 입원시 NIHSS 점수의분포는 0-2 점이 30.1%, 3-4 점이 19%, 5-8 점이 25.4%, 그리고 9점이상이 25.5% 이었다. 뇌졸중분류는 TOAST (Trial of Org in Acute Stroke Treatment) 분류로시행하였는데 LAD (large artery disease) 35.8%, SVD (small vessel disease) 24.6%, CE (cardioembolic) 8.7%, OD (other determined) 1.2%, UD (undetermined) 25.1% 이었으며일과성뇌허혈은 4.7% 으로관찰되었다. 급성기뇌경색치료법중에서경정맥혈전용해술은 3%, 항응고제는 19.2% 에서사용되었다. 퇴원시 MRDS 점수는 0-2 점까지가 58.5%, 3점이상이 41.5% 로측정되었다. 뇌동맥경화의분포는두개내동맥경화가 624 명 (66.0%), 두개외동맥경화가 106 명 (11.2%) 에서관찰되었으며두개내외의동맥경화가모두관찰된경우가 30명 (3.2%), 동맥경화가없는경우가 292 명 (30.9%) 이었다. 두개내동맥경화를증상유무에 따라분류하였을때증상성두개내동맥경화는 343명 (55%) 이었고무증상성두개내동맥경화는 281 명 (45%) 에서관찰되었다. 두개내동맥경화를개수에따라분류해보면, 한개의혈관에서동맥경화가관찰된경우가 291명 (46.7%), 두개는 154명 (24.7%), 그리고세개이상은 179 명 (28.7%) 로나타났다. 두개외동맥경화가한쪽에만있는경우는 90명, 양쪽이 16명이었다. 두개외동맥경화를정도에따라분류해보면중등도 15명, 고도 40명, 폐색 51명으로관찰되었다. 두개내동맥경화및두개외동맥경화의유무에따른요인들을비교하였다 (Table 1). 두개내동맥경화가있는환자들은두개내동맥경화가없는환자들에비해남자, 고혈압과당뇨가더많고, 흡연력, 음주력이높게나타났으며내원시 NIHSS 점수와퇴원시 MRDS 점수도중증이더많은것으로관찰되었다. 두개외동맥경화가있는환자들은없는환자에비해고지혈증과심방세동이더많고입원시 NIHSS 점수와퇴원시 MRDS 점수도중증인경우가더많은것으로관찰되었다. 관찰기간동안전체사망은 220 명 (23.8%) 이었으며뇌졸중과혈관질환이주된사망원인이었다. 두개외동맥경화환자에서상대적으로뇌혈관질환이아닌여타혈관질환사망의비중이높았다 (Table 2). 카플란마이어생존분석법을이용하여 Table 1. Clinical features according to the existence of ICAS and ECAS ICAS ECAS Yes = 624 No = 322 Yes = 106 No = 840 Age, mean±sd 65.8± ± ± ±11.8 Male, no (%) 322 (51.6)* 145 (45) 49 (46.2) 418 (49.8) Hypertension, no (%) 405 (64.9)* 193 (59.9) 75 (70.8)* 523 (62.3) DM, no (%) 293 (47) 118 (36.6) 43 (40.6) 368 (43.8) Hyperlipidemia, no (%) 115 (18.4) 68 (21.1) 11 (10.4) 172 (20.5) Atrial fibrillation, no (%) 56 (9) 31 (9.6) 17 (16) 70 (8.3) Ischemic heart disease, no (%) 60 (9.6) 33 (1 0.2) 14 (13.2) 79 (8.4) Alcohol, no (%) 180 (28.8) 110 (34.2) 35 (33) 255 (30.4) Smoking, no (%) 183 (29.3) 115 (35.7) 40 (37.7)* 258 (30.7) Previous stroke, no (%) 215 (34.4)* 87 (27) 47 (44.4) 255 (30.4) Prestroke prevention, no (%) 50 (8) 25 (7.8) 10 (9.4) 65 (7.7) Initial NIHSS score 0-2, no (%) 160 (25.6) 125 (38.8) 16 (15.1) 269 (32) 3-4, no (%) 115 (18.4) 65 (20.2) 19 (17.9) 161 (19.2) 5-8, no (%) 165 (26.4) 75 (23.2) 25 (23.6) 215 (25.6) >9, no (%) 184 (29.5) 57 (17.7) 46 (43.4) 195 (23.2) MRDS at discharge 0-2, no (%) 324 (51.9) 229 (71.1) 46 (43.4) 507 (60.4) >3, no (%) 300 (48.1) 93 (28.9) 60 (56.5) 333 (39.6) *p<0.2, p<0.05, ICAS; Internal carotid atherosclerosis, and ECAS; External carotid atherosclerosis. The chi square test, linear likely-hood test, linear by linear association test, and ANOVA test were used appropriately according to variable characteristics. 464

4 두개내동맥경화증이뇌경색이후의장기사망률에미치는영향 Figure 1. The survival probabilities of patients with ICAS (intracranial atherosclerosis) which is symptomatic or not were lower that of without ICAS (p<0.01). And survival probability of SICAS (symptomatic intracranial atherosclerosis) and ASICAS (asymptomatic intracranial atherosclerosis) did not differ statistically (p=0.147). 구한두개내동맥경화가있는환자들의사망률이두개내동맥경화가없는환자들에비해통계적으로의미있게높은것으로나타났다 (p<0.01, log rank test) (Table 3, Fig. 1). 시기에따라분석하면 30일째사망률은두개내동맥경화유무에영향을받지않으나 (p=0.356, chi-square test), 1년사망률은영향을받는것으로나왔다 (p=0.002, chi-square test). 두개외동맥경화가있는환자들의경우에도두개외동맥경화가없는환자들에비해높은사망률을보였다 (p<0.01, log rank test)(table 3, Fig. 2). 시기에따라분석하였을때도 30일과 1년사망률 모두두개외동맥경화가있는환자에서높게측정되었다 (p<0.01, chi-square test). 두개내동맥경화중에중등도이상의동맥경화가전방순환 (anterior circulation) 에서만관찰된환자는 254 명 (40.7%), 후방순환 (posterior circulation) 에서만관찰된환자는 149명 (23.9%), 그리고전방과후방순환둘다에서두개내동맥경화증이관찰된경우는 221 명 (35.4%) 이었고, 이들의사망률은각각 36.6%, 37% 와 46.4% 으로양쪽에동맥경화가같이있는경우에통계적으로유의하게높은사망률을보였다 (p< 0.01, log Table 2. The cause of death according to vascular lesion Total (n=220) ICAS (n=171) ECAS (n=41) Stroke, no (%) 133 (60.5%) 105 (61.4%) 22 (53.7%) MI and peripheral vascular disease, no (%) 19 (8.6%) 15 (8.8%) 8 (19.5%) Malignancy, no (%) 19 (8.6%) 11 (6.4%) 4 (9.8%) Others, no (%) 47 (21.4%) 38 (22.2%) 7 (17.1%) Undetermined, no (%) 2 (0.9%) 2 (1.2%) 0 (0%) Table 3. The cumulative mortality rate Cumulative mortality rate (%) 30 day 1 year 2 year 3 year 4 year 5 year ICAS (-) ICAS (+) ECAS (-) ECAS (+) CS (-) CS (+) ASICAS SICAS Number of ICAS CS; Cerebral atherosclerosis, ASICAS; Asymptomatic intracranial atherosclerosis, SICAS; Symptomatic atherosclerosis. J Korean Neurol Assoc Volume 25 No. 4,

5 강지훈장윤숙이준영김병건구자성권오현박종무이정주배희준 Figure 2. The patients with ECAS (extracranial atherosclerosis) had lower survival probabilities compared to those without ECAS (p<0.01). Figure 3. The more number of intracranial atherosclerosis is correlated with higher mortality rate (p<0.01). The 1,2, and 3 of the graph represent numbers of intracranial atherosclerosis. rank test). 증상성두개내동맥경화환자들의사망률은무증상성두개내동맥경화환자들의사망률간에는통계적으로유의한차이를보이지않았으나 (p=0.147, log-rank test)(table 3, Fig. 1), 두개내동맥경화개수와사망률의관계는, 동맥경화의수가한개, 두개, 그리고세개이상으로증가할수록높은사망률을보이는것으로나타났다 (p<0.01, log-rank test)(table 3, Fig. 3). 두개내동맥경화의유무, 개수, 증상유무및두개외동맥경화의유무를독립변수로보고시행한콕스회귀분석결과를표 4에제시하였다. 조분석에서는두개내동맥경화의유무, 정도및두개외동맥경화유무가모두통계적으로의미있게사망의위험을증가시켰으나나이, 뇌졸중기왕력, 허혈성심질환, 심방세동, TOAST 분류, 입원시 NIHSS 점수와퇴원시 MRDS 점수등교란변수를보정한후에는두개외동맥경화를제외하고는 95% 신뢰구간이 1을포함하여통계적인의미를상실하였다. 고찰 이연구는두개내동맥경화를갖는환자들의장기예후를평가하는연구로두개내동맥경화의존재유무, 증상유무와개수가사망률에미치는영향을평가하기위해시행하였다. 홍콩에서발표한두개내동맥경화의장기예후를평가한연구에서는두개내동맥경화와두개외동맥경화를모두가지는환자들의 2년후사망률이 26.4% 로동맥경화가없는환자들의사망률 12.8% 보다높았으나 (p=0.008, log rank test), 두개내동맥경화자체에대해서는사망률과의의미있는상관성을보여주지못하였다. 12 본연구에서는두개내동맥경화가있는환자와없는환자로나누어 5년사망률을평가하였는데카플란마이어생존분석에서는두개내동맥경화가있는환자들의사망률이높은것으로보였으나보정사망위험률이통계적으로유의성이없게나와두개내동맥경화가장기예후에독립적으로는영향을 466

6 두개내동맥경화증이뇌경색이후의장기사망률에미치는영향 미치는변수는아니라고생각할수있었다. 즉, 두개내동맥경화가독립적인나쁜예후인자는아니지만, 예후에관련된중요한인자로작용하는것을알수있었다. 이와는반대로두개외동맥경화의경우에는다변량분석이후에도지속적으로통계적으로유의하게높은사망률을보여두개외동맥경화는나쁜예후인자인것을확인하였다. NASCET (North American Symptomatic Carotid Endarterectomy Trial Collaborators) 연구와 ACAS (Asymptomatic Carotid Atherosclerosis Study) 연구는두개외경동맥에서같은정도의동맥경화율도증상유무에따라장기예후에다른영향을미친다는점을시사하였는데, 2,3 본연구에서는두개내동맥경화에서도이런현상이관찰되는지를알아보았다. 증상성두개내동맥경화환자와무증상성두개내동맥경화환자의사망률은통계적인차이가없어두개외동맥경화와는다르게증상유무와예후는관계가없다는것을알수있었다. 그러나무증상성두개내동맥경화도증상성두개내동맥경화와비슷한예후를보이고, 두개내동맥경화가없는환자들에비해높은사망률을보여무증상두개내동맥경화도임상적의미를두어야하겠다. 전술한홍콩연구에서는두개내동맥경화의개수가많을수록장기사망률에의미있는영향을미치는것으로나왔으나 11,12 이연구에서는두개내동맥경화의개수도단변량분석에서는통계적으로의미있는상관성을보였지만다변량분석후에는통계적의미를상실하여독립적인장기예후요인은아닌것으로나왔다. 이연구의단점으로첫째, 특정기관에입원한뇌졸중환자를대상으로하였다는점, 둘째, 장기예후를사망의측면에서만조사하였고, 뇌졸중의재발이나심근경색과같은여타혈관성질환의발병과같은임상사건의발생측면에서는자료를얻지못한점, 셋째, 동맥경화를뇌자기공명혈관조영술만으로검사한점, 마지막으로연구기간에입원한급성뇌졸중환자의약 28% 가주로뇌자기공명영상이없어제외되었다는점을지적할수있다. 셋째요인은뇌자기공명혈관조영술만으로평가하여뇌혈관조영술에비해정확성이떨어지며이전연구에비해두개내외에서동맥경화가모두관찰되는경우와다발성두개내동맥경화의수가더적게관찰되었으나, 16 뇌혈관조영술으로시행한연구의경우주요뇌동맥의동맥경화증으로인해혈관조영술을시행한경우가다수포함되어있을가능성이높아본연구와결과가다르게나온것으로생각되었다. 마지막요인은선택비뚤림으로연구결과의일반화에미치는영향이클수있어, 추가분석을시행하였다. 급성기뇌경색환자중에서뇌자기공명영상을촬영하지않은환자들과촬영한환자들의특성을 비교하여보았는데, 뇌자기공명영상촬영을하지않은사람들은촬영한사람에비해뇌졸중기왕력이많았고, 입원시 NIHSS 점수가높았고, TOAST 분류상 UD (48.6%) 가많았다 (p<0.01). 다른임상적인특성은유사하였다. 중증일경우에자기공명영상촬영을하지못한경우가많고이때문에 TOAST 분류도 UD 가많이나온것으로생각되었으며, 이로인해중증의 LAD 환자가상대적으로많이제외되어 LAD 의단기예후가좋은쪽으로치우쳤을가능성이있다. 두개내동맥경화가 30일후사망률에미치는영향이크지않았던것이설명된다고할수있다. 그러나두개외동맥경화의경우장단기예후에영향을미치는것으로나온점은상술한선택삐뚤림의크기가연구에타당성을손상할정도는아님을시사한다고판단되며, 모든급성뇌졸중환자에게뇌자기공명영상을얻기힘든현실또한결과해석시고려되어야할점이다. 결론적으로본연구의결과는두개내동맥경화는장기예후에영향을미치지않거나적어도독립적인위험요인이되지않음을시사한다. 또한증상유무나동맥경화개수도장기예후에독립적인영향을미치지않았다. 본연구가제기한의문에답이주어졌다고생각하지는않는다. 제기된연구의단점들을보완하기위해뇌자기공명영상촬영을비율을더높이고사망이외에심근경색, 뇌졸중재발등임상사건을조사하는다기관관찰연구가필요하다는생각이고두개내동맥경화가주요한뇌졸중의원인인우리나라에서이루어지기를기대한다. REFERENCES 1. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1998;339: Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991;325: Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273: Sacco RL, Kargman DE, Gu Q, Zamanillo MC. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 1995;26: Wityk RJ, Lehman D, Klag M, Coresh J, Ahn H, Litt B. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke 1996;27: Wong KS, Huang YN, Gao S, Lam WW, Chan YL, Kay R. Intracranial stenosis in Chinese patients with acute stroke. Neurology 1998;50: J Korean Neurol Assoc Volume 25 No. 4,

7 강지훈장윤숙이준영김병건구자성권오현박종무이정주배희준 7. Huang YN, Gao S, Li SW, Huang Y, Li JF, Wong KS et al. Vascular lesions in Chinese patients with transient ischemic attacks. Neurology 1997;48: Feldmann E, Daneault N, Kwan E, Ho KJ, Pessin MS, Langenberg P, et al. Chinese-white differences in the distribution of occlusive cerebrovascular disease. Neurology 1990;40: Marzewski DJ, Furlan AJ, St Louis P, Little JR, Modic MT, Williams G. Intracranial internal carotid artery stenosis: longterm prognosis. Stroke 1982;13: Klijn CJ, Kappelle LJ, Algra A, van Gijn J. Outcome in patients with symptomatic occlusion of the internal carotid artery or intracranial arterial lesions: a meta-analysis of the role of baseline characteristics and type of antithrombotic treatment. Cerebrovasc Dis 2001;12: Wong KS, Li H, Chan YL, Ahuja A, Lam WW, Wong A, et al. Use of transcranial Doppler ultrasound to predict outcome in patients with intracranial large-artery occlusive disease. Stroke 2000;31: Wong KS, Li H. Long-term mortality and recurrent stroke risk among Chinese stroke patients with predominant intracranial atherosclerosis. Stroke 2003;34: Adams HP Jr, Woolson RF, Biller J, Clarke W. Studies of Org in patients with acute ischemic stroke. TOAST Study Group. Haemostasis 1992;22: Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org in Acute Stroke Treatment. Stroke 1993;24: Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol 2000;21: Suh DC, Lee SH, Kim KR, Park ST, Lim SM, Kim SJ, et al. Pattern of atherosclerotic carotid stenosis in Korean patients with stroke: different involvement of intracranial versus extracranial vessels. AJNR Am J Neuroradiol 2003;24:

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1.. Volume 12, Number 1, 6~16, Factors influencing consultation time and waiting time of ambulatory patients in a tertiary teaching hospital Jee-In Hwang College of Nursing Science, Kyung Hee University :