Original Article Ewha Med J 2017;40(3): eissn 세사이에발생하는뇌경색의특징, 다기관레지스트리연구 장윤경, 송태진, 김

Original Article Ewha Med J 2017;40(3):128-135 https://doi.org/10.12771/emj.2017.40.3.128 eissn 2234-2591 18 30 세사이에발생하는뇌경색의특징, 다기관레지스트리연구 장윤경, 송태진, 김용재, 허지회 1, 이경열 1, 김영은 2, 장민욱 3, 조수진 3, 강석윤 3 이화여자대학교의과대학신경과학교실, 1 연세대학교의과대학신경과학교실, 2 한림대학교의과대학성심병원신경과학교실, 3 한림대학교의과대학동탄성심병원신경과학교실 Characteristics for Ischemic Stroke in 18 30 Years Old Patients, Multicenter Stroke Registry Study Yoonkyung Chang, Tae-Jin Song, Young-Jae Kim, Ji Hoe Heo 1, Kyung-Yul Lee 1, Young Eun Kim 2, Min Uk Jang 3, Soo-Jin Cho 3, Suk Yun Kang 3 Department of Neurology, Ewha Womans University School of Medicine, 1 Departments of Neurology, Yonsei University College of Medicine, Seoul, 2 Department of Neurology, Hallym University College of Medicine, Sacred Heart Hospital, Hallym University College of Medicine, Anyang, 3 Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea Objectives: Although there have been several reports that described characteristics for young age stroke, information regarding very young age (18 30 years old) has been limited. We aimed to analyze demographic factors, stroke subtype, and 3-month outcome in acute ischemic stroke patient who have relatively very young age in multicenter stroke registry. Methods: We evaluated all 122 (7.1%) consecutive acute ischemic stroke (within 7 days after symptom onset) patients aged 18 to 30 from 17,144 patients who registered in multicenter prospective stroke registry, 1997 to 2012. Etiology was classified by Trial of Org 10172 in Acute Stroke Treatment criteria. Stroke severity was defined as National Institutes of Health Stroke Scale (NIHSS) and stroke outcome was defined by modified Rankin scale (mrs) at 3 months after index stroke. Results: The mean age of all included patients was 25.1±3.7 years and 76 patients (62.2%) were male. The median NIHSS at admission was 4. Considering stroke subtype, 37 patients (30.3%) had stroke of other determined etiology (SOD), 37 (30.3%) had undetermined negative evaluation (UN) and 31 (25.4%) had cardioembolism (CE) were frequently noted. After adjusting age, sex and variables which had P<0.1 in univariable analysis (NIHSS and stroke subtype), CE stroke subtype (odds ratio, 4.68; 95% confidence interval, 1.42 15.48; P=0.011) were significantly associated with poor functional outcome (mrs 3). Conclusion: In very young age ischemic stroke patients, SOD and UN stroke subtype were most common and CE stroke subtype was independently associated with poor discharge outcome. (Ewha Med J 2017;40(3):128-135) Received January 15, 2017 Revised April 20, 2017 Accepted April 26, 2017 Corresponding author Suk Yun Kang Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, 7 Keunjaebong-gil, Hwaseong 18450, Korea Tel: 82-31-8086-2310, Fax: 82-31-8086-2317 E-mail: sukyunkang@hanmail.net Key Words Young age stroke; Cerebral infarction; Carotid artery, internal, dissection; Vertebral artery dissection; Undetermined negative etiology; Prognosis This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial 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. 128 THE EWHA MEDICAL JOURNAL

Ischemic Stroke in Very Young Patients 서론젊은나이에발생하는뇌경색은중, 장년때발생하는뇌경색과비교하여발생빈도도드물고뇌경색의주요원인도다르다 [1]. 젊은나이에발생하는뇌경색의주요원인은심장성색전증이거나비동맥경화성혈관질환으로상대적으로동맥경화증및소혈관질환으로인한뇌경색은드물다고알려져있다 [2,3]. 한편, 우리나라의뇌경색발생률은식생활습관의서구화와고혈압, 고지혈증등의위험인자가젊은나이에도불구하고많아짐에따라젊은나이에발생하는뇌경색의빈도가높아지고있다 [4]. 더구나, 이전에는 40 45 세미만의환자는동맥경화증및소혈관질환으로인한뇌경색이드물었지만최근에는기존의보고와비교하였을때상대적으로동맥경화증및소혈관질환으로인한뇌경색의발생빈도가높아지고있어뇌경색의주요원인및기전의분포도변화하고있을것으로추측된다 [5]. 따라서, 이전에는 40 45 세미만에서발생한뇌경색환자를젊은나이에발생하는뇌경색이라고생각했지만상대적으로좀더이른나이에발생하는뇌경색환자를 젊은나이에발생한뇌경색 으로다시고려하여뇌경색의특성을파악할필요가있다. 30 세이전의젊은성인은대학이나군대등의집단생활을할기회가많고, 결혼이나독립등의생활의변동기이다. 또한최근유럽에서시행된연구에서 30 세이전에발생한뇌졸중으로입원하는환자수가 1990 년대이후로계속증가되고있음이보고된바있다 [6]. 그러나, 아직까지우리나라에서이전기준보다이른나이, 즉 30 세이전에발생하는뇌경색환자의특성에대한연구는부족한실정이다. 이에본연구자들은다기관전향적레지스트리를이용하여 30 세이전에발생하는뇌경색환자의동반질환, 위험인자, 뇌경색의기전및예후에대해확인해보고자하였다. 방법 1. 대상및방법 1997 년 1월부터 2012 년 12 월까지서울, 경기및강원지역 8곳의대학병원에급성뇌경색으로입원한환자중에서나이가 30 세이하이고뇌경색관련증상발생 7일이내에각병원에내원하여뇌전산화단층촬영술 (computed tomography, CT) 또는뇌자기공명영상 (magnetic resonance imaging, MRI) 에서급성뇌경색으로진단되어입원한환자를후향적으로연구에포함하였다 [7-10]. 또한 31 44 세, 45 세이상의급성뇌경색환자와의뇌경색의아형을비교분석하기위해이화여자대학교목동병원에동일기간에입원한환자를연구에포함하였다. 본연구는각병원의임상시험윤리심사위원회로부터승인을받았으며후향적연구이기때문에동의서는받지않았다. 각병원의전향적레지스트리로부터본연구 에포함된환자중에서병원간중복되는환자는없었다. 모든대상환자는각병원의뇌경색영상프로토콜에따라뇌 CT, 뇌 MRI, 전산화단층혈관조영술 (computed tomography angiography, CTA), 자기공명혈관조영술 (magnetic resonance angiography, MRA), 필요시디지털감산혈관조영술 (digital subtraction angiography, DSA) 을시행하였다. 또한, 각병원마다기본적으로직업을포함한인구학적정보와과거력을파악하였고신체검사및신경학적진찰을시행하였다. 심전도검사, 흉부방사선촬영, 뇌 CT 또는뇌 MRI, MRA 및기본적인혈액검사를모든환자에서시행하였다. 뇌경색의원인이명확하지않은경우각병원의판단하에추가적으로 24 시간홀터검사, 경흉부초음파검사, 경식도초음파검사, 그리고호모시스테인, 항핵항체 (anti-nuclear antibody), 항중성구세포질항체 (anti-neutrophil cytoplasmic antibody) 와항카디오리핀항체 (anti-cardiolipin antibody) 를포함한자가면역항체, S단백질, C단백질, 항트롬빈결핍혹은기능저하관련혈액검사를추가로시행하였다. 뇌경색위험인자중고혈압은입원중안정시혈압이 140/90 mmhg 이상또는고혈압약을이미복용하고있던경우로정의하였다. 당뇨병의유무는내원당시공복혈당이 126 mg/dl 이상, 무작위로측정한혈당이 200 mg/dl 이상, 당화혈색소가 6.5% 이상그리고경구혹은주사제로혈당강하제를투여하고있던경우중에서한가지이상에해당할경우당뇨병이있다고정의하였다. 고지혈증은공복혈청총콜레스테롤수치가 240 mg/dl 이상또는저밀도콜레스테롤수치가 160 mg/dl 이거나고지혈증약을복용중인경우로하였다. 흡연력은뇌경색으로입원당시흡연중이었거나금연후 1년미만인경우로하였으며음주력은평소 1주일에 300 g 이상의에탄올을섭취하는경우로, 최근음주력은뇌경색발생 1주일이내에 300 g 이상의에탄올을섭취한경우로정의하였다 [8,11,12]. 직업은무직, 화이트칼라, 군인, 학생, 블루칼라로분류하였으며뇌경색발생시의상태는편의상깨어있었으나활동중이아니었을때 (resting), 운동을포함한동작을취하고있을때 (vigorous activity), 수면중또는기상시발견된경우 (sleep or wake-up) 로나누어분석을시행하였다. 뇌경색기전의분류는각병원모두 Trial of Org 10172 in Acute Stroke Treatment (TOAST) 분류를기준으로하였다 [13]. 두명의저자 (SYK, KYL) 가전체병원의자료및영상을취합하여독립적으로뇌경색기전을분류하였으며의견이불일치하는경우다른저자 (TJS) 와합의하에분류를하였다. TOAST 분류에의거하여뇌경색기전을각각큰동맥죽상경화증 (large artery atherosclerosis, LAA), 소혈관질환 (small vessel occlusion, SVO), 심장성색전증 (cardioembolism, CE), 다른원인뇌졸중 (stroke of other determined etiology, SOD) 및원인불명뇌졸중 (stroke of unde- THE EWHA MEDICAL JOURNAL 129

Chang Y, et al termined etiology) 으로나누었다. 원인불명뇌졸중은두가지이상의원인에의한경우 (two or more causes identified, UT), 원인미상 (negative evaluation, UN) 로다시나누었다. SVO 에는 UN 으로분류된환자에서관통동맥영역의열공경색이지만고전적열공증후군이아니거나뇌경색크기가 15 mm 이상이면서 20 mm 미만인경우 (n=2) 도포함하였다. SOD 중혈관박리는이전연구의방법을참조하여 CTA, MRA 또는 DSA 상에서뇌혈관에다음과같은소견중에하나이상이관찰될때로정의하였다 : 길게가늘어지는양상의혈관협착 (long tapered arterial stenosis), 길게가늘어지는양상의혈관폐쇄 (tapered occlusion), 가성동맥류 (pseudoaneurysm), 내막피판 (intimal flap), 이중내강 (double lumen), 벽내혈종 (intramural hematoma)[13,14]. 뇌경색의중증도는입원당시의미국국립보건원뇌졸중척도 (National Institute of Health Stroke Scale, NIHSS) 로정하였으며신경학적예후평가는 3개월째수정 Rankin 척도 (modified Rankin scale, mrs) 를이용하여평가하였다. mrs 는각병원에속한연구자또는연구간호사가대면또는전화로평가하였다. 2. 통계분석통계프로그램은 SPSS ver. 21.0 (IBM Corp, Armonk, NY, Table 1. Demographic and clinical data of included patients Variable mrs<3 (n=95) mrs 3 (n=27) Total (N=122) P-value Male sex 61 (64.2) 15 (55.6) 76 (62.3) 0.413 Age (yr) 25.1±3.8 24.8±3.3 25.1±3.7 0.646 Risk factor Hypertension 12 (12.6) 3 (11.1) 15 (12.3) 0.832 Diabetes mellitus 1 (1.1) 0 1 (0.8) 0.592 Dyslipidemia 8 (8.4) 0 8 (6.6) 0.119 Smoking 45 (47.4) 9 (33.3) 54 (44.3) 0.195 Regular alcohol intake 23 (24.2) 7 (25.9) 30 (24.6) 0.855 Recent alcohol intake 8 (8.4) 0 8 (6.6) 0.126 Atrial fibrillation 2 (2.1) 5 (18.5) 7 (5.7) 0.001 Occupation situation 0.140 Without routine job 13 (13.7) 7 (25.9) 20 (16.4) White collar 37 (38.9) 4 (18.9) 41 (33.6) Soldier 22 (23.2) 6 (22.2) 28 (23.0) Student 20 (21.1) 9 (33.3) 29 (23.8) Blue collar 3 (3.2) 1 (3.7) 4 (3.3) Activity at stroke occurrence 0.183 Resting 68 (71.6) 23 (85.2) 91 (74.6) Vigour activity 17 (17.9) 1 (3.7) 18 (14.8) Wake-up stroke 10 (10.5) 3 (11.1) 13 (10.7) Stroke classification 0.028 Large artery atherosclerosis 8 (8.4) 2 (7.5) 10 (8.3) Small vessel occlusion 7 (7.4) 0 7 (5.7) Cardioembolism 18 (18.9) 13 (48.1) 31 (25.4) Other determined etiology 30 (31.6) 7 (25.9) 37 (30.3) Undetermined negative 32 (33.7) 5 (18.5) 37 (30.3) NIHSS 3 (1 5) 12 (9 14) 4 (2 8) 0.001 Values are presented as mean±standard deviation, number (%), or median (interquartile range). mrs, modified Rankin scale at 3 months after index stroke; NIHSS, National Institute of Health Stroke Scale. 130 THE EWHA MEDICAL JOURNAL

Ischemic Stroke in Very Young Patients USA) 을사용하였다. 퇴원시의 mrs 를각각 0 2, 3 6으로나누어두군의인구학적특성, 위험인자, 발병당시의상황, 뇌경색기전의분류, NIHSS 를연속형변수들은 independent-test 또는 Mann-Whitney U test 로검정을시행하였고이분형, 명목형변수들은카이제곱검정또는 Fisher 의정확한검정을시행하여비교하였다. 퇴원시의 mrs 와관련되어있는독립적인인자를확인하기위해단변량로지스틱회귀분석에서 P값이 0.1 미만인변수와나이와성별을다변량로지스틱분석에보정하였다. 양측검정으로 P 값이 0.05 미만인경우를유의하다고정하였다. 결과 1. 인구학적특성, 검사시행빈도및위험인자비교본연구에서해당기간동안의 7곳의병원에급성뇌경색으로입원한환자는총 17,144 명이었으며이중에서 18 30 세이하에발생한환자는 122 명 (0.7%) 이었다 ( 이대목동병원 3,618 명중 21 명, 0.1%; 신촌세브란스병원 6,726 명중 58 명, 0.3%; 강남세브란스병원 1,923 명중 17 명, 0.1%; 한림대의료원 강남, 강동, 평촌, 한강, 춘천 4,877 명중 26 명, 0.2%). 본연구에포함된 122 명의평균나이는 25.1±3.7세였고, 남자는 76 명 (62.2%) 이었다. 뇌경색증상발생당시상황으로는깨어있었으나활동중이아니었을때뇌경색이발생한경우가 91 명 (74.6%) 로가장흔하였으며동작을취하고있을때 (14.8%), 수면중또는기상시발견된경우 (10.7%) 순으로빈도가높았다. 전체환자중 7명 (5.7%) 이정맥내혈전용해제를투여받았으며, 2명 (1.6%) 은정맥내혈전용해제투여및동맥내혈전용해술을, 1명 (0.8%) 은동맥내혈전용해술을시행받았다. 내원당시 NIHSS 의정중값은 4점 ( 사분위수 2 8) 이었다 (Table 1). 전체 122 명의환자중 24 시간홀터검사 47 명 (38.5%), 경흉부초음파검사 85명 (69.7%), 경식도초음파검사 76 명 (62.3%), 호모시스테인 67명 (54.9%), 항핵항체 84명 (68.9%), 항중성구세포질항체 83명 (68.0%) 와항카디오리핀항체 84명 (68.9%), S단백질 89 명 (73.0%), C단백질 89 명 (73.0%), 그리고항트롬빈결핍혹은기능저하관련혈액검사를 87명 (71.3%) 에게각각시행하였다. 2. 뇌졸중의아형, 원인, 예후전체 122 명중에서 37 명 (30.3%) 이 SOD, 37 명 (30.3%) 이 UN, 31 명 (25.4%) 이 CE, 10 명 (8.3%) 이 LAA, 7명 (5.7%) 이 SVO 로분류되었으며 UT 로분류된환자는없었다. SOD 의원인으로혈관박리가 21 명 (56.8%) 으로가장흔하였으며박리는두개외속목동맥에서 8명 (21.6%), 두개외척추동맥에서 6명 (16.2%), 두개내척추동맥에서 3명 (8.1%), 중뇌동맥에서 3명 (8.1%), 두개내 속목동맥에서 1명 (2.7%) 순으로높은빈도를보였다. 두개내속목동맥박리환자는박리가중뇌동맥까지연장되어있었다. 그다음으로는뇌수막염과동반된혈관염에의한뇌경색이흔하였으며 2명 (5.4%) 은나이세리아뇌수막염, 1명 (2.7%) 은결핵균, 1명 (2.7%) 은단순포진바이러스 2형이뇌척수액검사상에서원인병인으로확인되었다. 또한모아모야병이 4명 (10.8%), 타카야수혈관염이 3명 (8.1%), 전신홍반루푸스가 3명 (8.1%), Sneddon 증후군이 1명 (2.7%), 유전성단백 C, S 결핍이 1명 (2.7%) 에서관찰되었다 (Table 2). UN 으로분류된환자의경우모든환자에서혈관염을비롯한자가면역질환관련검사를시행하였으나특이소견이없었으며 37 명중 19명 (51.3%) 에서경식도초음파검사를시행하였고 29명 (78.3%) 이경흉부초음파검사를시행받았으나뇌경색과연관된이상소견이없었다. 또한 UN 으로분류된환자중에서 1명은임신중에뇌경색이발생하였으나검사상에특이소견이없었고또다른 1명은혈색소가 5.1 mg/dl 로측정되어내시경, 골수검사를비롯한빈혈에대한원인검사를시행하였으나철결핍성빈혈로판정되었다. CE 로분류된환자 31 명의환자중 14 명 (45.1%) 에서심방세동이관찰되었으며이중 11명은판막이상, 2명은확장심근병이함께관찰되었다. 다음으로 11명 (35.4%) 이열린타원구멍, 3명 (9.6%) 이감염성심내막염, 2명 (6.4%) 이심방중격결손, 1명 (3.2%) 이급성심근경색이동반되어있었다. 이대목동병원의전향적레지스트리에서 31 44 세, 45 세이상의급성뇌경색환자군과뇌경색의아형을비교하였을때 18 30세 Table 2. Causes for other determined etiology Variable Causes for other determined etiology (n=37) Arterial dissection 21 (56.8) Extracranial internal carotid artery 8 (21.6) Intracranial internal carotid artery* 1 (2.7) Extracranial vertebral artery 6 (16.2) Intracranial vertebral artery 3 (8.1) Middle cerebral artery 3 (8.1) Vasculitis meningitis 4 (10.8) Moyamoya diseases 4 (10.8) Takayasu s diseases 3 (8.1) Systemic lupus erythematosus 3 (8.1) Sneddon s syndrome 1 (2.7) Familial protein C, S deficiency 1 (2.7) Values are presented as number (%). *One patient had both right intracranial internal carotid artery and middle cerebral artery dissection. THE EWHA MEDICAL JOURNAL 131

Chang Y, et al 의환자들은유의하게 SOD 와 UN 군이많았으며 31 44 세, 45 세 이상급성뇌경색환자들은 LAA 및 SVO 아형이많았으며나이가많은군으로갈수록 LAA, SVO 가아형이많아지고 SOD 군은적어지는양상을보였다 (P=0.001)(Fig. 1, Supplementary Table 1). 전체환자 112 명중 106 명의환자 (94.6%) 에서뇌경색발생후 3개월때 mrs 를확인하였다. 이중에서 27 명 (25.4%) 이예후가좋지않았다 (mrs 3). 직업과신체활동여부, 기상시발생여부등은예후에차이가없었다. 뇌경색으로입원하여병원내에서사망한환자는총 6명 (4.9%) 이었다. 나이와성별, 단변량분석에서 P값이 0.1 미만의변수인 NIHSS 와뇌경색의아형을보정하여다변량로지스틱회귀분석을시행한결과 NIHSS( 교차비, 2.94; 95% 신뢰구간, 1.61 5.37; P=0.001) 와뇌경색의아형중 CE( 교차비, 4.68; 95% 신뢰구간, 1.42 15.48; P=0.011) 만이통계적으로유의하게뇌경색이후 3개월째의나쁜예후 (mrs 3) 와독립적으로연관되어있었다 (Table 3). 3. 남녀비교환자군을남자와여자로나누어비교하였을때, 흡연력 (63.2% vs. 13.0%, P=0.001) 은남자가흔하였고남자가활동중에발생한경우가더흔하였으나 (21.1% vs. 4.3%, P=0.013) 그외고혈 % 100 90 80 70 60 50 40 30 20 10 0 Large artery atherosclerosis Small vessel occlusion Cardioembolism Other determined etiology Undetermined two or more causes identified Undetermined negative 10 (8.3) 7 (5.7) 31 (25.4) 37 (30.3) 0 (0.0) 37 (30.3) Very young age (18 30 years) 39 (18.1) 42 (19.4) 44 (20.4) 42 (19.4) 12 (5.6) 37 (17.1) Young age (31 44 years) 754 (22.3) 729 (21.6) 838 (24.8) 170 (5.0) 422 (12.5) 468 (13.8) Above young age (>45 years) Fig. 1. Stroke subtype comparison for very young age (18 30 years old) with young age (31 44 years old) or above young age ( 45 years old). Values are presented as number (%). The stroke of other determined etiology and undetermined negative evaluation stroke subtype were more frequently noted in 18 30 years old patients than those of 31 44 years old and 45 years old. The frequency of large artery atherosclerosis and small vessel occlusion subtypes was increased in elderly groups (31 44 years old and 45 years old groups; P=0.001). 압, 당뇨, 고지혈증, 음주력, 그리고심방세동의동반빈도, 직업, 뇌경색의아형및뇌경색발생후 3개월째의 mrs 에차이가없었다. 고찰 본연구는주로 40 50 대이하의환자를대상으로한이전의연구와는다르게더젊은 30 세이하에서발생한뇌경색의원인, 아형및뇌경색발생후 3개월째의예후에대해확인하였다. 전체뇌경색환자중에서약 7.1% 의환자가 30 세이하에서뇌경색이발생하였으며뇌경색의아형중에서는 SOD 가가장흔하였고혈관박리가주요원인이었다. 뇌경색발생후 3개월째의예후는 CE 아형인경우좋지않았다. 45 세미만에서발생한뇌경색을대상으로한이전연구들에서가장흔한뇌경색의아형은 SOD, UN 순이었고다음으로는 CE 또는 LAA 였다 [3,15,16]. 15 29 세와 30 40 세사이에발생한뇌경색의아형을비교한이전보고에의하면 15 29 세군이 30 40세군보다상대적으로 SOD 가흔하였고 CE 의아형의빈도는큰차이가없었다 [3]. 18 44 세의한국인뇌경색환자를대상으로하였던이전연구에서는 SOD, LAA, CE 의순으로빈도가높았다 [5]. 그러나 30 세미만의환자만을대상으로뇌경색의아형을분석해보면 SOD, UN, CE 의순서로빈도가높았으며 [5] 이는우리의연구결과와유사하였다. 본연구에서가장흔한뇌경색의아형은 SOD 였으며그중에서도두개외척추동맥박리및척추동맥박리가흔하였다. 혈관의박리특히경부혈관의박리는청, 장년층에발생하는뇌경색의원인중 20% 에달한다고알려져있으며 [17], 본연구의 56.8% 보다낮 Table 3. Independent factors for poor functional outcome at 3 months (mrs 3) Variable Adjusted OR (95% confidence interval) P-value Male sex 1.41 (0.56 3.54) 0.455 Age (yr) 0.96 (0.84 1.09) 0.564 NIHSS 2.94 (1.61 5.37) 0.001 Stroke subtype Large artery atherosclerosis 1.53 (0.23 9.91) 0.652 Small vessel occlusion No case Cardioembolism 4.68 (1.42 15.48) 0.011 Other determined etiology 1.37 (0.38 4.86) 0.626 Undetermined negative Reference mrs, modified Rankin scale; OR, odds ratio; NIHSS, National Institute of Health Stroke Scale. 132 THE EWHA MEDICAL JOURNAL

Ischemic Stroke in Very Young Patients 은경향을보였는데이는우리연구가상대적으로더젊은사람만을연구에포함했기때문으로생각된다 [18]. 우리연구에서는경부혈관의박리뿐만아니라두개내혈관박리도있었다. 서양인에비해동양인에서는자발성두개내혈관박리가상대적으로흔하다고알려져있으며대개내경동맥의원위부에서중뇌동맥부위또는중뇌동맥단독으로발생한다 [19]. 본연구에서도두개내속목동맥박리환자가속목동맥부터중뇌동맥까지박리소견을보여이전의연구와일치하는양상을보였다. 뇌경색의아형중 CE 는예후가좋지않으며치명적일수있다고알려져있다 [20]. 젊은나이에발생하는 CE 의주요원인으로류마티스열의합병증으로인한판막질환을들수있다. 또한판막질환은심방세동과같은뇌경색의중요원인을흔히동반한다 [17]. 실제본연구에서도 CE 환자중의다수가판막질환을가지고있었으며대부분심방세동을동반하였다. 더구나본연구에서도 CE 환자는뇌경색발생후 3개월째의좋지못한예후와연관되어있었다. 따라서 30 세이하에서 CE 아형으로뇌경색이발생한경우에는예후가좋지못할수도있음을인지해야한다. 본연구에서는전체환자의 10.8% 가감염으로인한혈관염으로인해뇌경색이발생하였다. 이는이전연구의 45 세미만에서감염으로인한뇌경색의빈도가약 7% 였다는이전의연구와비교하였을때빈도가약간높았다 [21]. 또한감염의원인도 HIV 감염이가장중요한원인이었던이전연구와는달리 [21] 나이세리아뇌수막염이주요원인이었다. 나이세리아뇌수막염은젊은나이에발생한뇌수막염의흔한원인중의하나이고우리나라젊은성인의인후면봉채취에서흔히관찰되는균이다 [22]. 그러나, 나이세리아뇌수막염과동반된뇌경색환자의수가 2명에불과하여일반화하기에는무리가있으며이전연구에서나이세리아뇌막염이다른세균성뇌막염에비하여뇌졸중빈도가낮게보고되어서향후추가연구가필요하다 [23]. 외국의보고와본연구와주요원인에차이가있는것은아마도인종이서로다르고연구방법에도차이가있기때문에생긴것으로추측된다. 젊은나이에발생하는뇌경색에서모야모야병이차지하는빈도는 15% 에달한다고알려져있고일반적으로 10 대또는 30 40대에흔하다 [24]. 30 세이하를대상으로한본연구에서는모야모야병의빈도가 10.8% 였는데이는본연구에포함된연령대가모야모야병이상대적으로적게나타나는연령이기때문일수있다. 기상시발생하는뇌경색은보고에따라다르지만전체뇌경색중에서약 20% 정도로생각된다 [25]. 본연구에서는기상시에발생하는뇌경색이 10.7% 정도로빈도가낮았다. 이는본연구에포함된환자의연령대가상대적으로젊기때문에중, 장년층의뇌경색과주로연관되어있는고전적인뇌경색의위험인자및자율신경조절이상이상대적으로적었기때문이라생각된다. 또한본연구에서는운동을포함한동작을취하고있을때발생한뇌경색이전 체의약 14.8% 였다. 전향적레지스트리를통하여신체활동과뇌경색의관계를분석한이전연구에서는전체뇌경색환자중약 5% 정도가운동및무거운것을들어올리는등의동작을취한지수시간이내에뇌경색이발생할가능성이상대적으로동작을취하지않은환자군보다높다고보고하였다 [26]. 본연구와의차이는아마도연구에포함된연령대로부터기인하는것으로생각되며향후이부분에대한추가적인연구가필요하다. 본연구는몇가지제한점이있다. 첫째, 비록전향적레지스트리에서환자를포함하였지만후향적연구이고출혈성뇌졸중을포함하지못하였기때문에선택치우침이존재한다. 둘째, 여러병원의자료에서연구에포함된환자의수가적지않지만 30 세이하환자전체를대표하기에는수가부족하며하며모든병원이뇌경색의원인을감별하기위해일치된진단방법및검사를시행하지못하였다. 더구나연구방법의한계로동일기간에각병원에내원한 31 44 세, 45 세이상전체뇌경색환자의아형을포함한여러특성과비교하지못하여추후이에대한연구가필요하다. 셋째, 본연구의연구기간이약 15 년으로길었지만우리나라의전체뇌졸중환자군의특성의변화를반영하기에는연구에포함된환자의수가많지않아추가적인결과분석이어려웠다. 넷째, 젊은성인의뇌졸중의위험인자로고려되는낮은신체활동상태와비만등을확인하지못하였다. 다섯째, 뇌경색의분포와다발성, 양측성침범여부와두통, 어지럼증등의동반증상에대한정보를확인하지못하였다. 마지막으로뇌졸중발생당시상황에대한회상치우침이있을수있다. 따라서, 본연구의결과는신중하게해석되어야한다. 결론적으로, 본연구는 30 세이하에서발생하는뇌경색은전체의 7.1% 가량되며뇌경색의아형중 SOD 가가장흔하였고주요원인은혈관박리였음을보여주었다. 또한 CE 아형의경우뇌경색발생시 30 세이하임에도불구하고좋지않은예후와연관되어있었기때문에각별한주의가필요함을주지시켜준다. 감사의글 This research was supported by grants of Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2015R1D1A1A01057934), Korean Neurology Society and Korean Neurosonology Society. References 1. Kristensen B, Malm J, Carlberg B, Stegmayr B, Backman C, Fagerlund M, et al. Epidemiology and etiology of ischemic stroke THE EWHA MEDICAL JOURNAL 133

Chang Y, et al in young adults aged 18 to 44 years in northern Sweden. Stroke 1997;28:1702-1709. 2. Carolei A, Marini C, Ferranti E, Frontoni M, Prencipe M, Fieschi C. A prospective study of cerebral ischemia in the young: analysis of pathogenic determinants. The National Research Council Study Group. Stroke 1993;24:362-367. 3. Siqueira Neto JI, Santos AC, Fabio SR, Sakamoto AC. Cerebral infarction in patients aged 15 to 40 years. Stroke 1996;27:2016-2019. 4. Hong KS, Bang OY, Kang DW, Yu KH, Bae HJ, Lee JS, et al. Stroke statistics in Korea: part I. Epidemiology and risk factors: a report from the Korean Stroke Society and Clinical Research Center For Stroke. J Stroke 2013;15:2-20. 5. Kwon SU, Kim JS, Lee JH, Lee MC. Ischemic stroke in Korean young adults. Acta Neurol Scand 2000;101:19-24. 6. Tibæk M, Dehlendorff C, Jørgensen HS, Forchhammer HB, Johnsen SP, Kammersgaard LP. Increasing incidence of hospitalization for stroke and transient ischemic attack in young adults: a registry-based study. J Am Heart Assoc 2016;5:e003158. 7. Song TJ, Suh SH, Min PK, Kim DJ, Kim BM, Heo JH, et al. The influence of anti-platelet resistance on the development of cerebral ischemic lesion after carotid artery stenting. Yonsei Med J 2013;54:288-294. 8. Lee BI, Nam HS, Heo JH, Kim DI; Yonsei Stroke Team. Yonsei Stroke Registry: analysis of 1,000 patients with acute cerebral infarctions. Cerebrovasc Dis 2001;12:145-151. 9. Song TJ, Cho HJ, Chang Y, Choi K, Jung AR, Youn M, et al. Low plasma proportion of omega 3-polyunsaturated fatty acids predicts poor outcome in acute non-cardiogenic ischemic stroke patients. J Stroke 2015;17:168-176. 10. Lee BC, Hwang SH, Jung S, Yu KH, Lee JH, Cho SJ, et al. The Hallym Stroke Registry: a web-based stroke data bank with an analysis of 1,654 consecutive patients with acute stroke. Eur Neurol 2005;54:81-87. 11. Song TJ, Kim J, Lee HS, Nam CM, Nam HS, Kim YD, et al. Distribution of cerebral microbleeds determines their association with impaired kidney function. J Clin Neurol 2014;10:222-228. 12. Hillbom M, Numminen H, Juvela S. Recent heavy drinking of alcohol and embolic stroke. Stroke 1999;30:2307-2312. 13. 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 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41. 14. Provenzale JM, Sarikaya B. Comparison of test performance characteristics of MRI, MR angiography, and CT angiography in the diagnosis of carotid and vertebral artery dissection: a review of the medical literature. AJR Am J Roentgenol 2009;193:1167-1174. 15. Williams LS, Garg BP, Cohen M, Fleck JD, Biller J. Subtypes of ischemic stroke in children and young adults. Neurology 1997;49:1541-1545. 16. Putaala J, Metso AJ, Metso TM, Konkola N, Kraemer Y, Haapaniemi E, et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry. Stroke 2009;40:1195-1203. 17. Ghandehari K, Moud ZI. Incidence and etiology of ischemic stroke in Persian young adults. Acta Neurol Scand 2006;113:121-124. 18. Rubinstein SM, Peerdeman SM, van Tulder MW, Riphagen I, Haldeman S. A systematic review of the risk factors for cervical artery dissection. Stroke 2005;36:1575-1580. 19. Debette S, Compter A, Labeyrie MA, Uyttenboogaart M, Metso TM, Majersik JJ, et al. Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection. Lancet Neurol 2015;14:640-654. 20. Grau AJ, Weimar C, Buggle F, Heinrich A, Goertler M, Neumaier S, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke 2001;32:2559-2566. 21. Onwuchekwa AC, Onwuchekwa RC, Asekomeh EG. Stroke in young Nigerian adults. J Vasc Nurs 2009;27:98-102. 22. Durey A, Bae SM, Lee HJ, Nah SY, Kim M, Baek JH, et al. Carriage rates and serogroups of Neisseria meningitidis among freshmen in a university dormitory in Korea. Yonsei Med J 2012;53:742-747. 23. Bodilsen J, Dalager-Pedersen M, Schonheyder HC, Nielsen H. Stroke in community-acquired bacterial meningitis: a Danish population-based study. Int J Infect Dis 2014;20:18-22. 24. Kim JS. Moyamoya disease: epidemiology, clinical features, and diagnosis. J Stroke 2016;18:2-11. 25. Koton S, Tanne D, Bornstein NM, Investigators N. Ischemic stroke on awakening: patients characteristics, outcomes and potential for reperfusion therapy. Neuroepidemiology 2012;39:149-153. 26. Mostofsky E, Laier E, Levitan EB, Rosamond WD, Schlaug G, Mittleman MA. Physical activity and onset of acute ischemic stroke: the stroke onset study. Am J Epidemiol 2011;173:330-336. 134 THE EWHA MEDICAL JOURNAL

Ischemic Stroke in Very Young Patients Supplementary Table 1. Stroke subtype comparison for very young age with young age or above young age Stroke subtype Very young age (18 30 yr) n=122 Young age (31 45 yr) n=216 Above young age ( 46 yr) n=3,381 Large artery atherosclerosis 10 (8.3) 56 (25.9) 754 (22.3) Small vessel occlusion 7 (5.7) 47 (21.8) 729 (21.6) Cardioembolism 31 (25.4) 38 (17.6) 838 (24.8) Other determined etiology 37 (30.3) 38 (17.6) 170 (5.0) Undetermined negative 37 (30.3) 37 (17.1) 468 (13.8) Undetermined two or more causes identified 0 (0.0) 0 (0.0) 422 (12.5) P-value=0.001 by chi-square test (between very young age and young age, between very young age and above young age). THE EWHA MEDICAL JOURNAL 135