원저 http://dx.doi.org/10.17340/jkna.2015.2.2 순천향대학교의과대학순천향대학교부천병원신경과 Clinical Characteristics in Lacunar Infarction with Less Than 50% Stenosis in the Parent Artery Dong Hyun Lee, MD, Hyung-Jun Kim, MD, Seung-Geun Lee, MD, Jeong-Ho Park, MD, Sun-Ah Park, MD, Ki-Bum Sung, MD, Tae-Kyeong Lee, MD, PhD Department of Neurology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea Background: Contrary to the initial hypothesis, there is accumulating evidence that the pathogenesis of lacunar infarction (LI) is heterogeneous. LI is often accompanied by intracranial stenosis, and while the clinical significance of severe stenosis of the intracranial parent artery in LI has been demonstrated, that of mild stenosis in LI has not been. Thus the aim of this study was to determine the clinical relevance of mild intracranial stenosis in LI. Methods: Ninety-three consecutive patients with acute LI were enrolled between March 2011 and December 2013. The patients were divided according to the presence of intracranial stenosis in the parent artery into pure LI (PLI) and LI with mild intracranial stenosis (<50% stenosis, BAD). Various clinical and laboratory characteristics were compared between the two groups. Results: PLI group were older and, had a less frequent history of smoking, a larger infarct, lower likelihood of a favorable outcome, and higher National Institute of Health Stroke Scale score at discharge in the univariate analysis. After adjusting for confounding factors, BAD was associated with older age at onset [odds ratio (OR) = 1.113, 95% confidence interval (95% CI) = 1.056-1.172, p<0.001), no history of previous statin medication (OR = 13.362, 95% CI = 1.014-176.062, p=0.049), and nonsignificant stenosis in the parent artery was associated with larger infarct (β=0.296, p=0.01) in the multivariate analyses. Conclusions: LI with mild parent-artery disease was demonstrated to have distinct clinical characteristics compared to LI without parent artery disease. Thus, even mild branch atheromatous disease in LI should be evaluated thoroughly and treated via a planned and systematic approach. J Korean Neurol Assoc 33(2):82-88, 2015 Key Words: Acute ischemic stroke, Lacunar infarction, Intracranial atherosclerosis 서 론 열공경색은초기에관통동맥의지방유리질증 (lipohyalinosis) Received October 16, 2014 Revised December 10, 2014 Accepted December 10, 2014 Address for correspondence: Tae-Kyeong Lee, MD, PhD Department of Neurology, Soonchunhyang University Bucheon Hospital, #170 Jomaru-ro, Wonmi-gu, Bucheon 420-767, Korea Tel: +82-32-621-5220 Fax: +82-32-621-6950 E-mail: xorudoc@schmc.ac.kr 이나미세죽종 (microatheroma) 같이소동맥에국한된질환으로추정되었지만, 1,2 그후많은연구들을통해심장성색전증이나연관동맥 (relevant artery) 의죽상경화증과연관된협착에의해서도발생할수있음이알려졌다. 3-5 특히두개내뇌혈관의죽상경화가흔한동양인에서연관동맥의폐색혹은 50% 이상의유의한협착은열공경색의중요한원인이다. 6 소동맥질환이외의원인에의한열공경색은상대적으로신경학적예후가나쁘고, 뇌경색크기가크며, 고혈압과연관된경우가더흔하다. 7 그러나열공경색에서연관동맥의 50% 미만경도협착의임상적의 82 대한신경과학회지제 33 권제 2 호, 2015
미에대해서는연구가부족한실정이다. 따라서본연구에서는급성기열공경색으로내원한환자중연관동맥의협착이동반되지않은환자와 50% 미만의협착이동반된열공경색환자를대상으로한비교연구를통해연관동맥경도협착의임상적의미에대해알아보고자한다. 대상과방법 1. 대상 2011년 3월부터 2013년 12월까지본원신경과에발생 7일이내에뇌경색으로입원한환자를대상으로하였다. 모든뇌경색환자에서입원중본원의뇌경색영상프로토콜에따라뇌 CT, 뇌MRI, 전산화단층혈관조영술 (CTA) 혹은자기공명혈관조영술 (MRA) 을시행하였고, 인구학적정보, 과거력, 임상증상에대한문진, 심전도검사, 흉부방사선촬영, 혈액검사같은전신상태평가도하였다. 그리고심장성색전증에대한평가를위한흉부경유심장초음파를하였다. 뇌혈관질환위험인자중고혈압은입원중안정시혈압이 140/90 mmhg 이상또는고혈압약을이미복용하고있던경우로정의하였으며당뇨병은내원당시공복혈당이 126 mg/dl 이상이거나당뇨약을복용하고있던경우로하였다. 고지혈증은공복혈청총콜레스테롤수치가 240 mg/dl 이상또는저밀도콜레스테롤수치가 160 mg/dl이거나고지혈증약을복용중인경우로하였다. 흡연력은재발당시흡연을하고있거나금연후 1년미만인경우로하였다. 뇌경색기전의분류는 Trial of Org 10172 in Acute Stroke Treatment (TOAST) 분류에따라, 8 큰동맥죽상경화증 (large artery atherosclerosis, LAA), 소혈관질환 (small vessel occlusion, SVO), 심장성색전증 (cardioembolism, CE), 다른원인뇌졸중 (stroke of other determined etiology, SOD) 및원인불명뇌졸중 (stroke of undetermined etiology) 으로나누었다. 원인불명뇌졸중은두가지이상의원인에의한경우 (two or more causes, UT), 원인미상 (negative evaluation, UN), 불완전검사 (incomplete evaluation, UI) 로세분하였다. 전체환자중에서열공경색환자를선별하기위해서뇌MRI를시행하지않았거나 TOAST분류에서 LAA, CE, 원인불명중 UT와 UI를제외하였다. 그리하여 SVO로분류된환자이외에도원인불명중 UN으로분류된환자에서관통동맥영역의열공경색이지만, 고전적열공증후군이아니거나뇌경색크기가 15 mm 이상인경우도대상환자에포함시켰다. 뇌경색의중증도는미국국립보건원뇌졸중척도 (National Institute of Health Stroke Scale, NIHSS) 로입원당시, 1일, 3일, 퇴원시에각각기록하였다. 퇴원시임상경과는수정Rankin척도와바텔지수를이용하여평가하였다. 양호한임상경과의기준은퇴원시수정Rankin척도가 0 또는 1이면서바텔지수가 95점이상인경우로정의하였다. 2. 방법 CTA나 MRA로부터얻은뇌혈관영상에서열공경색의연관동맥중두개내모동맥 (parent artery) 에동맥경화에의한 50% 미만의협착이확인되면정도에관계없이 branch atheromatous disease (BAD) 군으로정의하였고 (Fig. B), 협착이확인되지않고정상뇌혈관을보이면 pure lacunar infarction (PLI) 군으로정의하였다 (Fig. A). 두개내혈관의협착정도의측정은 WASID 연구에서사용되었던방식을적용하였고, 9 두명의공동저자 (H-J Kim, S-K Lee) 가각각독립적으로측정하였으며의견이불일치하는경우제1저자 (DH Lee) 의의견을따랐다. 두군모두에서 MRI의확산강조영상에서관찰된뇌경색병변의단면이가장큰슬라이스에서긴직경의크기를 0.1 mm 단위까지측정 A B Figure. Illustrative cases of PLI group (A) and BAD group (B) are shown in the diffusion weighted imaging and intracranial time-of-flight MR angiography. PLI; pure lacunar infarction, BAD; branch atheromatous disease. White arrow shows less than 50% stenosis of left middle cerebral artery. J Korean Neurol Assoc Volume 33 No. 2, 2015 83
하여뇌경색크기로정의하였다. BAD군과 PLI군의인구학적특성, 혈관위험인자, 약물복용력, 진단검사의학검사, 뇌경색의크기, 입원중신경학적악화유무, 입퇴원당시의 NIHSS 점수, 퇴원시임상경과를비교하여유의한차이가있는지확인하였다. 이어서, 유의한차이가있는변수들을보정하여 BAD군과 PLI군에서차이를보이는변수를다변량분석으로찾아내었다. 의수준은 p 값 0.05 이하로하였다. 결과 본연구에선별된총환자는 93명이었고, 그중정상뇌혈관을보였던 PLI군이 51명, 두개내연관동맥의 50% 미만의경도의협착증을보였던 BAD군은 42명이었다 (Table 1). 3. 통계두군에서비교한여러변수들중연속형변수들은스투덴트 t-검정혹은 Mann-Whitney U 검정을시행하였고, 이분형변수들은카이제곱검정혹은 Fisher 정확검정을시행하였다. 다변량분석은변수의속성을고려하여이분형변수는로지스틱회귀분석을이용하였고, 연속형변수는다중선형회귀분석을이용하였다. 통계프로그램은 SPSS version 17.0을사용하였고, 통계적유 1. 인구학적인자와혈관위험인자 (Table 1) 모동맥협착이동반된군은연령대가높았고 ( 평균 ± 표준편차 : 54.0±11.75 vs 69.8±11.38, p<0.001), 성별의차이는관찰되지않았다. 고혈압, 당뇨병, 고지혈증의과거력은두군간에유의한차이는없었지만, 고혈압약복용력이 BAD 군에서높았고 (57.1% vs 31.4%, p=0.012), 흡연자의비율은 PLI 군에서현저 Table 1. Comparison of demographic, clinical, radiological characteristics in 93 patients classified according to the existence of stenosis in the intracranial relevant artery PLI group (n=51) BAD group (n=42) p-value Age (years) 54.0±11.75 69.8±11.38 <0.001 Gender (n, %) 34 (66.7) 22 (52.4) 0.161 Hypertension (n, %) 34 (66.7) 35 (83.3) 0.068 Diabetes mellitus (n, %) 20 (39.2) 23 (54.8) 0.135 Hyperlipidemia (n, %) 4 (7.8) 7 (16.7) 0.214 Smoking (n, %) 24 (47.1) 7 (16.7) 0.002 Previous antiplatelet agent (n, %) 9 (17.6) 12 (28.6) 0.210 Previous statin (n, %) 4 (7.8) 1 (2.4) 0.373 Previous anti-hypertensives (n, %) 16 (31.4) 24 (57.1) 0.012 Previous anti-diabetics (n, %) 8 (15.7) 11 (26.2) 0.211 WBC count (/mm 3 ) 7,867±2,505.3 7,188±1,664.5 0.122 Hemoglobin (g/dl) 14.3±1.54 13.5±1.69 0.038 Hematocrit (%) 41.1±3.79 39.3±4.69 0.044 Platelet (x10 3 /mm 3 ) 221±53.3 224±53.3 0.817 ESR (mm/hour) 14±17.5 18±20.5 0.335 Total cholesterol (mg/dl) 179±44.4 182±35.7 0.673 Triglyceride (mg/dl) 162±91.5 133±68.5 0.088 HDL cholesterol (mg/dl) 45±11.3 47±12.7 0.536 LDL cholesterol (mg/dl) 112±38.6 119±26.3 0.363 Initial glucose (mg/dl) 151±71.7 171±76.1 0.209 Infarct size (cm) 1.13±0.549 1.49±0.762 0.010 Worsening or fluctuation (n, %) 6 (11.8) 9 (21.4) 0.207 Initial NIHSS score 2 (1.0-3.0) 3.0 (1.0-4.0) 0.325 Discharge NIHSS score 0 (0.0-2.0) 2 (1.0-4.0) 0.006 Favorable outcome at discharge * (n, %) 34 (66.7) 19 (45.2) 0.038 Values are presented as mean±sd unless otherwise indicated. Modified Rankin scale 1 and Barthel index score 95. PLI; pure lacunar infarction, BAD; branch atheromatous disease, WBC; white blood cell, ESR; erythrocyte sedimentation rate, HDL; high density lipoprotein, LDL; low density lipoprotein, NIHSS; national institute of health stroke scale. 84 대한신경과학회지제 33 권제 2 호, 2015
Table 2. Analysis of relevant contributing factors to be a BAD group compared to a PLI group Odds ratio 95% confidence interval p-value Age (years) 1.113 1.056-1.172 <0.001 Previous anti-diabetic medication 0.801 0.233-2.760 0.725 Previous anti-hypertensive medication 2.001 0.665-6.023 0.217 Previous statin medication * 0.075 0.006-0.986 0.049 Smoking 0.545 0.158-1.884 0.338 Result by logistic regression analysis, adjusting factors: age, previous history of taking anti-diabetic medication, anti-hypertensives, and statin medication, smoking. * Statin-naïve patient has about thirteen times higher probability to be a BAD group. BAD; branch atheromatous disease, PLI; pure lacunar infarction. Table 3. Analysis of contributing factors related to the size of infarction Unstandardized coefficients (B) Standardized coefficients (beta) p-value Age (years) -0.052-0.107 0.353 NIHSS score at discharge 1.344 0.370 0.001 Non-significant stenosis 3.987 0.296 0.010 Previous anti-hypertensive medication 0.105 0.008 0.941 Previous anti-platelet agent medication -0.388-0.024 0.817 Previous statin medication 7.453 0.251 0.011 Smoking 3.438 0.242 0.020 Unfavorable outcome at discharge 1.444 0.107 0.322 Result by multiple linear regression analysis (adjusted R 2 =0.31), adjusting factors: age, NIHSS score at discharge, non-significant stenosis in the parent artery, previous history of taking anti-hypertensives, anti-platelet agent and statin medication, smoking, unfavorable outcome at discharge. NIHSS; national institute of health stroke scale. 히높았다 (47.1% vs 16.7%, p=0.002). 항혈소판제, 고지혈증약, 당뇨병약복용력의차이는없었다. 2. 뇌MRI, MRA 결과와임상경과 (Table 1) 열공경색의크기는 BAD군이 PLI군보다통계학적으로유의하게컸다 ( 평균 ± 표준편차 : 1.49 ± 0.762 cm vs 1.13 ± 0.549 cm, p=0.010). BAD군과 PLI군간에내원당시 NIHSS 점수의차이가없었고, 입원중신경학적악화혹은변동에서도차이가없었지만, BAD군이퇴원시 NIHSS 점수가높았으며 ( 중위수 [ 사분범위 ]: 2 [1.0-4.0] vs 0 [0.0-2.0], p=0.006) 좋은임상경과를보이는비율이낮았다 (45.2% vs 66.7%, p=0.038). 3. 다변량분석결과단변량분석에서두군간에통계학적으로유의한차이를보였던연령, 흡연여부, 고혈압약복용력, 그리고임상적으로죽상경화증의경과에영향을줄수있는고지혈증약과당뇨병약복용력이두개내연관동맥질환이있는열공경색에대한기여인자로작용하는지로지스틱회귀분석을이용하여분석하였다 (Table 2). 단변량분석에서차이를보였던흡연력은두개내연관동맥질환여부에유의한영향을주지못했다. 연령은나이가 1살증가할때마다약 1.1배 BAD군에속할가능성이높았고 (Odds Ratio [95% CI] 1.113 [1.056-1.172], p<0.001), 고지혈증약복용력이없는사람일수록약 13배 BAD군에속할가능성이높았다 (Odds Ratio [95% CI] 13.362 [1.014-176.062], p=0.049). 뇌경색의크기와두개내연관동맥질환의연관성을확인하기위해서뇌경색의크기를종속변수로하고단변량분석에서유의한차이를보였던인자들을보정하여다중선형회귀분석을시행하였다 (Table 3). 뇌경색의크기에영향을줄수있는다른인자들을보정하더라도두개내연관동맥에 50% 미만의협착이뇌경색의크기와밀접한상관관계를갖고있었다 (β=0.296, p=0.01). 단변량분석에서차이를보였던퇴원시양호한임상경과는퇴원시임상경과를종속변수로하여로지스틱회귀분석을한결과, 두개내연관동맥질환유무가임상경과에영향을주지않았다 (Odds ratio [95% CI] 2.138 [0.680-6.727], p=0.194, Data not shown). 고찰 본연구는이전의연구들과는달리확실한심장성색전증의인자가있는경우뿐만아니라연관동맥에 50% 이상의협착혹은폐색이있어서 TOAST 분류상 LAA 또는 UT가되는경우를제외하였고, 비연관 (non-relevant) 동맥에만협착혹은폐색이있 J Korean Neurol Assoc Volume 33 No. 2, 2015 85
는경우도제외하여, 다른알려진원인없이관통동맥영역의뇌경색이발생한환자를대상으로하였다. 또한두개외연관동맥의죽상경화가동맥 -동맥색전증(artery-to-artery embolism) 으로열공경색을일으킬가능성 10 을배제하기위해서두개외혈관에만죽상경화가있는경우도제외하였다. 따라서전형적인열공경색환자의특성을선별적으로분석하였다는장점이있다. 이전열공경색연구에서별도로분류하지않았던 50% 미만의경도의협착이동반된열공경색환자를선별하여협착이전혀없는관통동맥질환으로발생한열공경색환자와비교함으로써협착이없는열공경색환자와위험인자의차이가있고, 뇌경색의크기도유의하게큰것을확인하였다. 허혈뇌졸중의공통된위험인자로잘알려진고혈압, 당뇨병, 고지혈증의과거력은두군간에유의한차이를보이지않았으나, BAD군의평균연령이약 16세가많았고, 흡연자는 PLI 군에서높았다. 고령은두개내혈관의죽상경화증의잘알려진위험인자이다. 무증상협착증이나이가들수록증가하는것이알려져있다. 11,12 단변량분석에서는 BAD군에서상대적으로고혈압의유병률이높은경향을보였고, 고혈압약을복용했던병력이유의하게높았다. 그러나, 다른변수를보정했을때에는두군간에유의한차이를보이지않았는데, 이는고혈압이두개내혈관의죽상경화증에관여하는위험인자일뿐만아니라, 13 열공뇌경색의공통적인위험인자이기때문으로생각한다. 흡연은경동맥의죽상경화증에주요한위험인자로알려졌지만, 두개내혈관죽상경화증과의관계는불확실한상태이다. 흡연은관통동맥과같은소동맥에서일산화질소의활성을억제하여, 14 혈관내피세포의손상을유발하고혈액-뇌장벽의기능을저해시킬수있다. 15 혈액- 뇌장벽의기능저하는혈관주변의뇌조직에세포외액의저류, Virchow-Robin공간의확장으로이어져열공경색의지방유리질증과섬유소모양괴사 (fibrinoid necrosis) 의병리를낳게된다. 16 열공경색을대상으로뇌경색크기에따른위험인자의차이를분석한최근의연구결과에서도흡연이지방유리질증으로인한열공경색과연관되어있을가능성이제시된적이있다. 17 하지만, 동양인에서인구집단을기반으로한무증상두개내혈관협착의유병률과위험인자를분석한대규모연구결과에서는흡연과의유의한연관성은없었다. 18 본연구에서도모동맥의죽상경화가동반되어있어분지죽상질환에의한열공경색의가능성이높은 BAD군에비해 PLI군에서흡연의빈도가높았다. 그러나, 두개내연관동맥질환의동반여부에흡연력이영향을주지않았고 (Odds Ratio [95% CI] 0.545 [0.158-1.884], p=0.338), 뇌경색의크기와의연관성을본다변량분석에서는오히려양의상관관계를보이는상반된결과로 나와서경동맥과마찬가지로두개내혈관의죽상경화증에도위험인자로작용할가능성이있어이에대한추가연구가필요할것으로보인다. 고지혈증약스타틴은지질강하효과이외에도혈관내염증반응의억제, 죽상경화의감소, 혈관내피세포의기능개선, 혈전생성억제등의다양한효과를통해서관상동맥질환, 뇌경색에예방효과가있음이잘알려져있다. 19,20 본연구에서는다른인자를보정하더라도스타틴제제를복용하지않은환자일수록 BAD군즉, 두개내연관동맥의협착이동반되어있을가능성이 13배높음을알수있었다. 대상환자수가작기는하지만스타틴제제를투여하고두개내뇌혈관의협착을추적관찰한연구에서, 21,22 스타틴제제가두개내혈관의죽상경화를방지할가능성이있음을보여본논문의연구결과를뒷받침할수있다. 열공경색에서죽상경화가모동맥에있는경우분지죽상폐색 (branch atheromatous occlusion) 이나미세죽종 (microatheroma) 에의한관통동맥폐색으로뇌경색이발병할가능성이높고, 이경우열공경색의크기는 5-20 mm로알려져있다. 23 한편모동맥에죽상경화가없이관통동맥의원위부에서지방유리질증으로도뇌경색이발병하는데, 이경우열공경색의크기가 7 mm 를넘지않는다. 24 분지죽상질환은관통동맥의입구 (orifice) 가모동맥죽상경화에의해직접막히거나, 죽상경화반이모동맥에서관통동맥의입구로확장되면서막히거나, 미세죽종이관통동맥의입구에서생겨막히면서열공경색을일으킨다. 25 모동맥의협착이경미한경우에는모동맥죽상경화의연장보다는미세죽종에의한관통동맥입구의폐색이열공뇌경색을일으키는주된기전일가능성이있다. 일반적으로오랜기간의고혈압에의한혈관손상으로발생하는지방유리질증은관통동맥의뇌실질내경로를따라분절성해체 (segmental disorganization) 를유발하므로뇌경색의크기가작다. 따라서미세죽종이관통동맥의입구를폐색하는경우지방유리질증에의한열공경색보다크기가클것으로예상할수있다. 본연구결과에서연관동맥의협착과뇌경색의크기는다른유의한인자들을보정하더라도밀접한상관관계가있었다 (β= 0.294, p=0.01). PLI군은모동맥을포함한뇌혈관이정상이었으므로분지죽상질환보다는관통동맥의지방유리질증이열공경색발병의주된기전으로추측할수있고, 모동맥의경미한죽상경화가있는 BAD군에서는미세죽종의관통동맥입구폐색이뇌경색발병에기여했을것으로추정할수있다. 50% 미만의협착증은 TOAST분류에서뇌경색의주요인자로인정하지않고있다. 8 그러나모동맥의죽상경화는협착정도에관계없이분지죽상질환의일환으로열공뇌경색의원인이될수있다. 26,27 기저동맥이 MRA에서정상이었던교뇌경색환자의약 40% 에 86 대한신경과학회지제 33 권제 2 호, 2015
서기저동맥의죽상경화반이존재함을고해상도 MRI로확인했던연구결과 28 도이를뒷받침한다. 심장성색전증이나경동맥협착증의증거없이중대뇌동맥의관통동맥영역에뇌경색이발생한 201명의환자들을대상으로한최근의연구에서연관동맥에협착이없는군보다협착이있는군에서뇌경색의직경이컸다. 27 하지만이연구에서는두개내연관동맥이 50% 이상협착을보였던환자들도협착이있는군에포함이되었고, 이와는달리본연구에서는 TOAST분류에서이러한환자들은 LAA나 UT로제외되어서경도의협착이있는환자들만포함되었다는차이점이있다. 단변량분석에서유의하게 BAD군이 PLI군보다퇴원시 NIHSS점수가높았고, 퇴원시양호한임상경과를덜취했지만, 연령을비롯한다른인자들을보정했을때는통계학적으로유의한차이를보이지않았다. 이전연구에서잠재적원인이없이열공경색이발병한군이심장성색전증, 큰동맥죽상경화증등의잠재적원인이있는열공경색군보다입원당시높은 NIHSS 점수, 퇴원 3개월후불량한임상경과를보였다. 7 모동맥질환이동반된열공경색과동반되지않은열공경색의임상경과를비교한연구 29 에서입원당시 NIHSS 점수와입원중신경학적악화혹은변동의비율에서차이가없었으나, 1년이내뇌경색재발은모동맥폐색이동반된군에서유의하게많았다. 그러나이연구는모동맥질환을모동맥폐색이있는경우로국한하였기에, 본연구보다중증도가높고, 임상경과가상대적으로더불량했을가능성이있다. 일반적으로열공경색환자의단기간임상경과는전반적으로양호한데, 23 본연구에서는퇴원후장기간임상경과에대한추적정보가없어서두군에서유의한차이를보이지않았을수도있다. 따라서연관동맥경도협착에따른열공경색의예후에대해서는장기간의추적관찰을통한추가연구가필요하다. 본연구에서 50% 미만의모동맥죽상경화유무가열공경색의단기간신경학적임상경과에영향을미치지않았다. 그러나, 50% 미만의모동맥죽상경화가동반된경우환자의나이가유의하게많았고, 흡연자의비율이낮은경향을보였고, 뇌경색의크기가컸다. 이러한결과는경미한모동맥의죽상경화가동반된열공경색은정상뇌혈관을보였던열공경색과는다른기전에의해뇌경색이발생했을가능성을시사한다. 모동맥의경미한죽상경화도분지죽상경화기전에의해뇌경색을유도했을가능성이있다. 분지죽상질환에의한열공경색은재발률이높고예후가좋지않아큰동맥죽상경화증의아형으로보고있다는점을고려할때, 경미한죽상경화를동반한열공경색도순수관통동맥질환에의한열공경색보다는적극적인진단과치료계획의대상이어야한다. 26,27 본연구는몇가지제한점이있다. 첫째, 두개내혈관의협착정도를단일검사가아니고 CTA 또는 MRA로부터얻은영상에서측정하여두검사방법간의차이로오차가발생했을가능성이있다. 하지만두개내혈관협착을측정하는데있어서 CTA 가 MRA에비해서민감도와양성예측도가낮지않아, 30 오차가있다고하더라도본연구결과에영향을줄수있는정도는아니라고생각한다. 둘째, 모든영역의열공경색환자를대상으로선정하여줄무늬체섬유막영역, 시상영역, 교뇌영역등다양한부위에서발생한열공경색이포함되었다. 따라서동일한크기의열공경색이발생하였다하더라도신경학적결손정도에상당한차이가있을수있고, 특히시상영역에서발생한뇌경색의경우 NIHSS 점수로는신경학적결손정도를정확히반영하지못하였을가능성이있다. 본연구는 50% 미만의모동맥협착을동반한열공경색에서도분지죽상질환이발병기전이될가능성이있음을제시하였다. 임상적으로는열공경색환자에서모동맥의폐색이나중등도이상의협착이없이경미한죽상경화가있더라도작은동맥질환으로치부하고소극적인진단과치료에머무르는것보다는숨겨져있는큰동맥죽상경화증의증거를찾고적극적인치료전략을세우는것이중요하다. REFERENCES 1. Fisher CM. The arterial lesions underlying lacunes. Acta Neuropathol 1968;12:1-15. 2. Fisher CM. Lacunes: Small, Deep Cerebral Infarcts. Neurology 1965; 15:774-784. 3. Mast H, Thompson JL, Voller H, Mohr JP, Marx P. Cardiac sources of embolism in patients with pial artery infarcts and lacunar lesions. Stroke 1994;25:776-781. 4. Adachi T, Kobayashi S, Yamaguchi S, Okada K. MRI findings of small subcortical "lacunar-like" infarction resulting from large vessel disease. J Neurol 2000;247:280-285. 5. Horowitz DR, Tuhrim S, Weinberger JM, Rudolph SH. Mechanisms in lacunar infarction. Stroke 1992;23:325-327. 6. Bang OY, Heo JH, Kim JY, Park JH, Huh K. Middle cerebral artery stenosis is a major clinical determinant in striatocapsular small, deep infarction. Arch Neurol 2002;59:259-263. 7. Baumgartner RW, Sidler C, Mosso M, Georgiadis D. Ischemic lacunar stroke in patients with and without potential mechanism other than small-artery disease. Stroke 2003;34:653-659. 8. 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. 9. Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol 2000;21:643-646. 10. Tejada J, Diez-Tejedor E, Hernandez-Echebarria L, Balboa O. Does a J Korean Neurol Assoc Volume 33 No. 2, 2015 87
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