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1 원저접수번호 :09-029(2 차 -0710) 경동맥스텐트삽입술후뇌혈관예비능의변화 : 6 개월추적관찰연구 경상대학교의학전문대학원신경과학교실 a, 영상의학과교실 b, 경남권역심뇌혈관센터 c 손승남 a,c 정희정 a 최대섭 b,c 김록범 c 김영수 a 김수경 a,c 강희영 a 박기종 a 권오영 a 임병훈 a,c 최낙천 a,c Changes in Cerebral Vascular Reserve Capacity after Carotid Artery Stenting: A 6-Month Follow-up Study Seungnam Son, MD a,c, Hee-Jeong Jeong, MD a, Dae Seob Choi, MD b,c, Rock-Bum Kim, MD c, Youngsoo Kim, MD a, Soo-Kyoung Kim, MD a,c, Heeyoung Kang, MD a, Ki-Jong Park, MD a, Oh-Young Kwon, MD a, Byeong Hoon Lim, MD a,c, Nack-Cheon Choi, MD a,c Departments of Neurology a and Radiology b, Gyeongsang National University School of Medicine, Jinju, Korea Kyungnam Regional Cardiocerebrovascular Center c, Jinju, Korea Background: Assessment of cerebral vascular reserve capacity prior to carotid artery stenting is used for predicting hyperperfusion syndrome. However, the changes in vascular reserve capacity after carotid stenting are not fully understood. In this study we investigated the effects of carotid artery stenting on the restoration of vascular reserve capacity using 99m TC-hexamethylpropylene amine oxime (HMPAO) single-photon-emission computed tomography (SPECT). Methods: The study population comprised 29 patients who underwent carotid artery stenting. Patients were divided into groups according to occlusion of the contralateral internal carotid artery (unilateral group vs bilateral group) and according to the presence or absence of symptoms related to carotid stenosis (symptomatic group vs asymptomatic group). Pre- and postacetazolamide-activated 99m TC-HMPAO SPECT were performed prior to stent insertion and at 1 and 6 months postoperatively. Vascular reserve capacity was assessed based on pre-, and 1- and 6-month postacetazolamide gamma count ratio (Post0, Post1, and Post6, respectively) and cerebrovascular reactivity (CVR0, CRV1, and CRV6, respectively). Results: The postacetazolamide gamma count ratio and cerebrovascular reactivity tended to improve at 1 month after stenting, but tended to deteriorate at 6 months after stenting in the unilateral group compared with the bilateral group [Post0-Post1=0.045±0.078 (mean±sd), p=0.014; Post0-Post6=0.025±0.063, p=0.042; Post1-Post6=-0.020±0.047, p=0.102; CVR0-CVR1=0.043±0.071, p=0.008, CVR0-CVR6=0.019±0.063, p=0.097; CVR1-CVR6=-0.024±0.047, p=0.008] and in the symptomatic group compared with the asymptomatic group (Post0-Post1=0.058±0.106, p=0.038; Post0-Post6= 0.048±0.103, p=0.061; Post1-Post6=-0.010±0.048, p=0.700; CVR0-CVR1=0.037±0.083, p=0.074; CVR0-CVR6=0.014±0.073, p=0.344; CVR1-CVR6=-0.023±0.054, p=0.055). Conclusions: The observed increases in postacetazolamide gamma count ratio and cerebrovascular reactivity at 1 month followed by decreases at 6 months may reflect the restoration of vascular reserve capacity. Carotid artery stenting can improve vascular reserve capacity, especially in patients with unilateral stenosis and with symptomatic stenosis. J Korean Neurol Assoc 29(4): , 2011 Key Words: Carotid stenosis, Carotid artery stenting, Cerebral perfusion, 99m TC-HMPAO SPECT, Vascular reserve capacity Received April 2, 2011 Revised May 11, 2011 Accepted May 11, 2011 *Nack-Cheon Choi, MD Department of Neurology, Gyeongsang National University School of Medicine, 90 Chiram-dong, Jinju , Korea Tel: Fax: brevis1@naver.com 서론 경동맥협착증은뇌경색의중요한위험인자로 1 다양한형태의뇌졸중과직접적인연관이있다. 따라서뇌경색의예방을위한경동맥협착증의수술치료또는중재시술이활발히시행되고 J Korean Neurol Assoc Volume 29 No. 4,

2 손승남정희정최대섭김록범김영수김수경강희영박기종권오영임병훈최낙천 있는데스텐트삽입술의경우내막절제술에비해덜침습적이고간편하다는장점이있다. 2-4 내막절제술이나스텐트삽입술전뇌혈관반응도 (cerebrovascular reactivity; CVR) 측정을통한뇌혈관예비능 (cerebrovascular reserve capacity) 평가는주로수술이나, 시술후발생할수있는과관류증후군 (hyperperfusion syndrome) 의예측을위해시행된다. 경동맥협착증환자에서양측대뇌반구사이의혈류불균형은잘알려져있으며 5,6 경동맥의협착정도가심할수록뇌혈관예비능이감소하며과관류증후군의발생빈도가증가한다는것역시여러연구를통해밝혀졌다 그러나내막절제술이나스텐트삽입술시행후뇌관류상태의변화에관하여는여전히논란이많으며 특히뇌혈관예비능의경우시술직후부터회복된다고하지만장기간추적관찰시의변화에대한정보는많지않다 또한양측경동맥에협착이나폐쇄가있는군과편측에만협착이나폐쇄가있는군사이의뇌혈류역학이다른경향을보이며, 25 무증상경동맥협착환자와증상협착환자사이의뇌관류역시차이가있음은 26 이전의연구를통하여알려져있으나이런변수들이뇌혈관예비능의회복에미치는영향에대해서는알려진바가적다. 저자들은경동맥협착증이있는환자를대상으로스텐트삽입술을시행하며시술전, 시술 1개월후, 시술 6개월후각각단일광자방출컴퓨터단층촬영 (technetium Tc 99m hexamethylpropyleneamine oxime brain single photon emission computed tomography, SPECT) 을촬영하였다. 대상환자를반대측경동맥의폐쇄유무와증상유발여부에따라구분하여경동맥스텐트삽입술전, 후의뇌혈류상태와뇌혈관반응도를평가하였다. 이를통하여경동맥스텐트삽입술이후의뇌혈관예비능회복에이러한변수들이미치는영향을조사하였다. 대상과방법 1. 대상 명을제외하였으며 3회의 SPECT 를모두시행하지않은 22명역시제외하고 29명이본연구에포함되었다. 스텐트삽입술은신경영상의학전문의한명이시행하였으며시술중모든환자에게색전방지기구 (FilterWire EZ TM, Boston Scientific, Natick, MA, USA) 를사용하였다. 스텐트삽입술시행도중이나추적관찰기간동안증상을유발한뇌경색이발생한환자는없었다. 대상환자를반대측경동맥의폐쇄유무에따라편측협착군 (unilateral group, n=24) 과양측협착군 (bilateral group, n=5) 으로구분하였으며또한증상의유무에따라무증상군 (asymptomatic group, n=10) 과증상군 (symptomatic group, n=19) 으로구분하였다. 2. SPECT 촬영및분석 SPECT 는스텐트삽입술전 (median: -11 일, range: -62~ -1일 ) 과삽입술후 1개월째 (median: 31일, range: 20~71 일 ), 그리고삽입술후 6개월째 (median: 192 일, range: 175~262 일 ) 에시행하였으며 Multi-SPECT3 (Simens inc., Hoffman estate, IL, USA) 기종을이용하였다. Acetazolamide (ACZ) 부하 SPECT 는기저영상과부하영상을하루에시행하는프로토콜을이용하여 ACZ 를투여하기전 (pre-acz-spect) 과투여후 (post-acz-spect) 에각각촬영하였다. Pre-ACZ-SPECT 는 99m Tc-HMPAO 740MBq 를주입하고 5분뒤에촬영을시작하여 20분간촬영하였으며 99m Tc-HMPAO 740MBq 주입 13분후에 ACZ 1 g 을주입하였다. Post-ACZ-SPECT 는 pre-acz-spect 촬영이끝나는시점에다시 99m Tc-HMPAO 740MBq를투여하고 5분뒤에촬영을시작하여 20분간촬영하였다. 정량분석을위해 5 mm 간격으로촬영한각환자의 SPECT 전체횡단면영상 24장중에서정중에위치한세장의연속된영상에대한감마수치를얻었다. 관심영역 (region of interest, ROI) 은대뇌반구를방사형으로 4부위로나누어양측중간대뇌동맥영역에해당하는 2부위를정하였다 (Fig. 1). 이연구는 2004 년 7월부터 2009 년 11월까지두개외경동맥협착증으로경동맥스텐트삽입술을시행한환자를대상으로하였다. 한쪽근위부내경동맥이나원위부총경동맥에스텐트삽입술을시행한환자들은시술전뇌혈관예비능평가를위하여 SPECT 를촬영하였으며추적관찰기간중재협착여부와혈류회복정도를확인하기위하여시술 1개월, 6개월째에연속하여 SPECT 를하였다. 연구기간동안경동맥스텐트삽입술을시행한전체환자는 59명이었으나양측에모두경동맥스텐트삽입술을시행한 3명과원위부내경동맥에스텐트삽입술을시행한 5 3. 비교변수각 ROI 의감마수치를이용하여감마수치비 (gamma count ratio, GCR) 를구하였다. GCR 은양측대뇌반구간의혈류량의비율로, 스텐트삽입술을시행하지않은쪽의감마수치에대한스텐트삽입술을시행한쪽의감마수치의비율로정하였다 (GCR=gamma counts of MCA territory in stent insertion side/gamma counts of MCA territory in contralateral side). 또한 ACZ 에대한뇌혈관반응도의평가를위하여각촬영시기 296 대한신경과학회지제 29 권제 4 호, 2011

3 경동맥스텐트삽입술 후 뇌혈관예비능의 변화: 6개월 추적관찰연구 99m Figure 1. Report of TC-HMPAO SPECT. Each report contains the pre- and post- acetazolamide activated SPECT gamma counts of 3 consecutive transverse slices of 5 mm thickness. We divided cerebral hemisphere by four regions radically, the region of interest (ROI) was defined the territories of middle cerebral arteries (B or D). The gamma counts of MCA territories (red box) were used for calculation of gamma count ratio (B/D or D/B, according to the stent insertion site). Table 1. Demographics and risk factors in 29 carotid stent patients Age (yr) Degree of stenosis (%) Sex (M/F) Hypertension DM Hypercholesterolemia Smoking Prior TIA/Stroke Heart problem Unilateral (n=24) 65.75± ± / Bilateral (n=5) 66± ±0.08 4/ Asymptomatic (n=10) 64.38± ±0.09 8/ Symptomatic (n=19) 66.82± ± / 의 ACZ 부하 전후의 모든 영상에 대한 GCR을 구하였다(Fig. 1). 화에 따른 값의 변화량 (Pre0-Pre1, Pre0-Pre6, Pre1-Pre6, 촬영 시기에 따라 pre-acz-spect의 GCR을 시술 전을 Pre0, Post0-Post1, Post0-Post6, Post1-Post6, CVR0-CVR1, 시술 후 1개월째를 Pre1, 시술 후 6개월째를 Pre6으로, 그리고 CVR0-CVR6, CVR1-CVR6)을 Wilcoxon signed rank test를 post-acz-spect의 GCR을 시술 전을 Post0, 시술 후 1개월 이용하여 분석하였다. 모든 분석에서 통계적 유효성은 p-value 째를 Post1, 시술 후 6개월째를 Post6으로 하였다. 가 0.05 미만인 경우로 설정하였다. 또한 저자들은 각 촬영시기의 pre-acz-spect의 GCR에서 post-acz-spect의 GCR을 뺀 값으로 뇌혈관반응도(CVR= 결 과 GCR of pre-acz-spect-gcr of post-acz-spect)를 구 하였는데 촬영시기에 따라 시술 전을 CVR0, 1개월째를 CVR1, 대상환자 29명 중 남자가 24명, 여자가 5명이었고, 나이 분 그리고 6개월째를 CVR6으로 하였다. 그러므로 뇌혈관반응도가 포는 52-78세(평균 65.79±6.09세)였다. 심혈관계 위험인자는 음의 값이면 상대적으로 뇌혈관예비능이 좋은 것을 의미한다. 고혈압이 24명(82.76%), 당뇨병 10명(34.48%), 고지혈증 7명 (24.14%), 흡연력 9명(31.03%), 과거 일과성허혈발작이나 뇌경 4. 통계분석 색 병력 4명(13.79%), 관상동맥질환이나 심방세동 같은 심장 질환 9명(31.03%)이었다(Table 1). 통계분석은 SPSS 13.0을 사용하였고 각 군별로 촬영시기 변 J Korean Neurol Assoc Volume 29 No. 4,

4 손승남정희정최대섭김록범김영수김수경강희영박기종권오영임병훈최낙천 Table 2. Values of each parameter in the unilateral group and in the bilateral group Unilateral Group Bilateral Group Max Min Mean±SD Max Min Mean±SD Pre ± ±0.179 Pre ± ±0.304 Pre ± ±0.350 Post ± ±0.161 Post ± ±0.296 Post ± ±0.307 CVR ± ±0.065 CVR ± ±0.056 CVR ± ±0.031 Max; Maximum value of each parameter, Min; Minimum value of each parameter, Pre0; Gamma count ratio of pre-acetazolamide SPECT at pre-procedure, Pre1; Gamma count ratio of pre-acetazolamide SPECT at 1 month after procedure, Pre6; Gamma count ratio of pre-acetazolamide SPECT at 6 months after procedure, Post0; Gamma count ratio of post-acetazolamide SPECT at pre-procedure, Post1; Gamma count ratio of post-acetazolamide SPECT at 1 month after procedure, Post6; Gamma count ratio of post-acetazolamide SPECT at 6 months after procedure, CVR0; Gamma count ratio of pre-acetazolamide SPECT at pre-procedure - Gamma count ratio of post-acetazolamide SPECT at pre-procedure, CVR1; Gamma count ratio of pre-acetazolamide SPECT at 1 month after procedure - Gamma count ratio of post-acetazolamide SPECT at 1 month after procedure, CVR6; Gamma count ratio of pre-acetazolamide SPECT at 6 month after procedure - Gamma count ratio of post-acetazolamide SPECT at 6 month after procedure. 후와 6개월후의 GCR (Post1-Post6) 은통계학적의미는없었지만감소하였다 (-0.014±0.046, p=0.205). 뇌혈관반응도는삽입술전과 1개월후비교 (CVR0-CVR1) 에서의미있게향상되었고 (0.030±0.073, p=0.045) 삽입술전과 6개월후의비교 (CVR0-CVR6) 에서도통계적유의성은보이지않았지만향상되었으나 (0.001±0.064, p=0.355) 오히려 1개월후와 6개월후의비교 (CVR1-CVR6) 에서는의미있게악화되었다 ( ±0.047, p=0.015). Figure 2. The mean values and changing slope of cerebrovascular reactivity (CVR) at each stage. The CVR was calculated as gamma count ratio of pre-acetazolamide SPECT minus gamma count ratio of post-acetazolamide SPECT. Therefore, the negative value of CVR means relatively good vascular reserve capacity and the downward slope between the stages means the improvement of vascular reserve capacity. 2. 편측협착군과양측협착군에서 SPECT 시행시기에따른각값의변화편측협착군과양측협착군에서의각값은 Table 2에기록하였다. 1. 전체환자에서 SPECT 시행시기에따른각수치들의변화전체환자를대상으로한분석에서 Pre-ACZ-SPECT GCR 은시기에따라증가하였으나통계적유의성은보이지않았다 (Pre0-Pre1=0.013±0.078, p=0.395: Pre0-Pre6: 0.019±0.085, p=0.285: Pre1-Pre6=0.006±0.044, p=0.509). Post-ACZ-SPECT 의 GCR 은삽입술전과삽입술 1개월후의 GCR (Post0-Post1) 이의미있게증가하였으나 (0.043±0.094, p=0.033) 삽입술전과 6개월후의 GCR (Post0-Post6) 비교에서는증가하였으나통계적유의성은없었으며 (0.028±0.090, p=0.115) 1개월 1) 편측협착군편측협착군을대상으로한분석에서 Pre-ACZ-SPECT GCR 은시기에따라증가하였으나통계적유의성은없었다. Post- ACZ-SPECT 의 GCR 은삽입술전과삽입술 1개월후의 GCR (Post0-Post1) 이의미있게증가하였고 (0.045±0.078, p=0.014) 역시삽입술전과 6개월후의 GCR (Post0-Post6) 에서도의미있게증가하였다 (0.025±0.063, p=0.042). 그러나 1개월후와 6개월후의 GCR (Post1-Post6) 은통계학적의미는없었지만감소하였다 (-0.020±0.047, p=0.102). 뇌혈관반응도는삽입술전과 1개월후비교 (CVR0-CVR1) 에서의미있게향상되었고 (0.043±0.071, p=0.008) 삽입술전과 6개월후의비교 298 대한신경과학회지제 29 권제 4 호, 2011

5 경동맥스텐트삽입술후뇌혈관예비능의변화 : 6 개월추적관찰연구 Table 3. Changes of each parameter in the unilateral group and in the bilateral group Unilateral Group Bilateral Group Mean±SD p-value Mean±SD p-value Pre0-Pre ± ± Pre0-Pre ± ± Pre1-Pre ± ± Post0-Post ± a 0.034± Post0-Post ± a 0.044± Post1-Post ± ± CVR0-CVR ± a ± CVR0-CVR ± ± CVR1-CVR ± a ± Pre0; Gamma count ratio of pre-acetazolamide SPECT at pre-procedure, Pre1; Gamma count ratio of pre-acetazolamide SPECT at 1 month after procedure, Pre6; Gamma count ratio of pre-acetazolamide SPECT at 6 months after procedure, Post0; Gamma count ratio of post-acetazolamide SPECT at pre-procedure, Post1; Gamma count ratio of post-acetazolamide SPECT at 1 month after procedure, Post6; Gamma count ratio of post-acetazolamide SPECT at 6 months after procedure, CVR0; Gamma count ratio of pre-acetazolamide SPECT at pre-procedure-gamma count ratio of post-acetazolamide SPECT at pre-procedure, CVR1; Gamma count ratio of pre-acetazolamide SPECT at 1 month after procedure-gamma count ratio of post-acetazolamide SPECT at 1 month after procedure, CVR6; Gamma count ratio of pre-acetazolamide SPECT at 6 month after procedure -Gamma count ratio of post-acetazolamide SPECT at 6 month after procedure. a p<0.05. Table 4. Values of each parameter in the asymptomatic group and in the symptomatic group Asymptomatic Group Symptomatic Group Max Min Mean±SD Max Min Mean±SD Pre ± ±0.118 Pre ± ±0.188 Pre ± ±0.201 Post ± ±0.172 Post ± ±0.212 Post ± ±0.215 CVR ± ±0.100 CVR ± ±0.618 CVR ± ±0.052 Max; Maximum value of each parameter, Min; Minimum value of each parameter, Pre0; Gamma count ratio of pre-acetazolamide SPECT at pre-procedure, Pre1; Gamma count ratio of pre-acetazolamide SPECT at 1 month after procedure, Pre6; Gamma count ratio of pre-acetazolamide SPECT at 6 months after procedure, Post0; Gamma count ratio of post-acetazolamide SPECT at pre-procedure, Post1; Gamma count ratio of post-acetazolamide SPECT at 1 month after procedure, Post6; Gamma count ratio of post-acetazolamide SPECT at 6 months after procedure, CVR0; Gamma count ratio of pre-acetazolamide SPECT at pre-procedure - Gamma count ratio of post-acetazolamide SPECT at pre-procedure, CVR1; Gamma count ratio of pre-acetazolamide SPECT at 1 month after procedure - Gamma count ratio of post-acetazolamide SPECT at 1 month after procedure, CVR6; Gamma count ratio of pre-acetazolamide SPECT at 6 month after procedure - Gamma count ratio of post-acetazolamide SPECT at 6 month after procedure. (CVR0-CVR6) 에서도향상되었으나 (0.019±0.063, p=0.097) 오히려 1개월후와 6개월후의비교 (CVR1-CVR6) 에서는의미있게악화되었다 (-0.024±0.047, p=0.008)(fig. 2, Table 3). 2) 양측협착군양측협착군을대상으로한분석에서는 Pre-ACZ-SPECT GCR 은시기에따라증가하였으나통계적유의성은없었으며 Post-ACZ-SPECT 의 GCR 역시시기에따라증가하였으나통계적유의성은없었다. 뇌혈관반응도도시기에따라악화되었으나통계적유의성은없었다 (Fig. 2, Table 3). 3. 무증상군과증상군에서 SPECT 시행시기에따른각값의변화무증상군과증상군에서의각값은 Table 4에기록하였다. 1) 무증상군무증상군을대상으로한분석에서는 Pre-ACZ-SPECT GCR 은시기에따라감소하였으나통계적유의성은없었다. Post-ACZ-SPECT 의 GCR은삽입술전과삽입술 1개월후 (Post0-Post1) 가증가하였고 (0.014±0.061, p=0.446) 삽입술전과 6개월후 (-0.009±0.039, p=0.574), 1개월후와 6개월 J Korean Neurol Assoc Volume 29 No. 4,

6 손승남정희정최대섭김록범김영수김수경강희영박기종권오영임병훈최낙천 Table 5. Changes of each parameter in the asymptomatic group and in the symptomatic group Asymptomatic Group Symptomatic Group Mean±SD p-value Mean±SD p-value Pre0-Pre ± ± Pre0-Pre ± ± Pre1-Pre ± ± Post0-Post ± ± a Post0-Post ± ± Post1-Post ± ± CVR0-CVR ± ± CVR0-CVR ± ± CVR1-CVR ± ± Pre0; Gamma count ratio of pre-acetazolamide SPECT at pre-procedure, Pre1; Gamma count ratio of pre-acetazolamide SPECT at 1 month after procedure, Pre6; Gamma count ratio of pre-acetazolamide SPECT at 6 months after procedure, Post0; Gamma count ratio of post-acetazolamide SPECT at pre-procedure, Post1; Gamma count ratio of post-acetazolamide SPECT at 1 month after procedure, Post6; Gamma count ratio of post-acetazolamide SPECT at 6 months after procedure, CVR0; Gamma count ratio of pre-acetazolamide SPECT at pre-procedure - Gamma count ratio of post-acetazolamide SPECT at pre-procedure, CVR1; Gamma count ratio of pre-acetazolamide SPECT at 1 month after procedure - Gamma count ratio of post-acetazolamide SPECT at 1 month after procedure, CVR6; Gamma count ratio of pre-acetazolamide SPECT at 6 month after procedure - Gamma count ratio of post-acetazolamide SPECT at 6 month after procedure. a p<0.05. 후의비교에서는감소하였으나 (-0.023±0.043, p=0.123) 통계적의의는없었다. 뇌혈관반응도는삽입술전과 1개월후의비교 (CVR0-CVR1) 에서향상되었고 (0.015±0.047, p=0.406) 1개월후와 6개월후의비교 (CVR1-CVR6) 에서는악화되었으나 (-0.015±0.031, p=0.141) 삽입술전과 6개월후의비교 (CVR0-CVR6) 에서는큰변화가없었다 (0.000±0.043, p=1.000) (Fig. 2, Table 5). 2) 증상군증상군을대상으로한분석에서는 Pre-ACZ-SPECT GCR 은시기에따라증가하였으나통계적유의성은없었다. Post-ACZ- SPECT 의 GCR 은삽입술전과삽입술 1개월후 (Post0-Post1) 가의미있게증가하였고 (0.058±0.106, p=0.038) 삽입술전과 6개월후 (Post0-Post6) 에서도증가하였다 (0.048±0.103, p=0.061). 그러나 1개월후와 6개월후의 GCR (Post1-Post6) 은통계적의미는없었지만감소하였다 (-0.010±0.048, p= 0.700). 뇌혈관반응도역시삽입술전과 1개월후비교 (CVR0-CVR1) 에서향상되었고 (0.037±0.083, p=0.074) 삽입술전과 6개월후의비교 (CVR0-CVR6) 에서도향상되었으나 (0.014±0.073, p=0.344) 오히려 1개월째와 6개월째의비교 (CVR1-CVR6) 에서는악화되었다 (-0.023±0.054, p=0.055)(fig. 2, Table 5). 고찰 본연구를통하여저자들은스텐트삽입술후뇌혈관반응도가시술후초기에는증가하고이후시간이지나며감소하지만시 술전에비해서는증가한상태로유지되며이러한변화는반대측경동맥폐쇄가없는환자군에서두드러지며증상성경동맥협착환자군에서역시통계적유의성은없지만유사한경향이나타남을확인하였다. 내막절제술이나스텐트삽입술시행후뇌혈관예비능의호전을보고한연구는주로두개경유초음파 (transcranial Doppler, TCD) 와 기능자기공명영상 (functional MRI) 19,24 을이용하였다. 그러나이연구들은증상협착환자만을대상으로하였거나, 19,24 증상과무증상환자를모두포함하였더라도증상군과무증상군에대한각각의분석을시행치않았으며, 반대측경동맥의심한협착이나폐쇄가있는군을제외하였거나 19,21 따로분석하지않아 20,22-24 본연구결과와직접비교할수없다. 또한대부분의연구가시술직후, 22 1주일이내, 19 또는 1-2 개월째 24 시행한 1회의검사결과와수술 / 시술전의결과를비교한것이기때문에장기간추적관찰시의뇌혈관예비능의변화를알기가어렵다. TCD 이용하여숨참기검사법 (breath-holding test) 으로스텐트삽입술시술전, 시술 6시간이후, 그리고시술 30일후의뇌혈관예비능을측정한연구 ( 증상성 : 54, 무증상성 : 6, 반대편협착 / 폐쇄 : 45) 에서뇌혈관예비능은시술직후부터호전되어 30일까지지속되었으며 20 역시 TCD 를이용한숨참기검사법으로시술전과시술 2일후, 그리고시술 2-4 개월후의뇌혈관예비능을측정한연구 ( 증상성 : 13, 무증상성 : 16, 반대편협착 / 폐쇄 : 7) 에서도뇌혈관예비능은시간이지날수록호전되었다. 23 그러나반대측경동맥협착이나폐쇄가없거나동측의원위부경동맥이나중간대뇌동맥의협착이없는환자를대상으로하여 300 대한신경과학회지제 29 권제 4 호, 2011

7 경동맥스텐트삽입술후뇌혈관예비능의변화 : 6 개월추적관찰연구 양전자방출단층촬영 (positron emission tomography, PET) 을이용하여시술전, 시술 1-7 일후, 그리고시술 3-4 개월후뇌관류변화와대사를조사한연구 ( 증상성 : 5, 무증상성 : 11) 에서는본연구의결과와유사한경향을보였다. 27 이연구에서안정시뇌혈류량과뇌관류압 (cerebral perfusion pressure, CBF/CBV), 그리고뇌산소대사비 (cerebral metabolic rate of oxygen, CMRO 2) 는시술 1-7일후증가하다가시술 3-4개월후감소하였으나시술전에비해서는증가하였다. 또한 ACZ 주입후뇌혈류의변화량으로예측한뇌혈관예비능은점차증가하는것으로나타났다. 저자들은이러한결과가뇌혈관자동조절능이시술직후에는제대로작동하지못하다가시간이지나며회복되어나타나는현상으로판단하였다. 그러나각각의변수변화를본연구의결과와비교하면차이가있다. 먼저편측협착군과증상군에서안정시뇌혈류량을반영하는 Pre-ACZ-SPECT GCR 은시기에따라증가하는것으로나타났으며오히려뇌혈관예비능을반영한다고판단할수있는 Post-ACZ-SPECT GCR 과뇌혈관반응도가 1개월째에향상되었다가 6개월째악화되는것으로나타났다. 이런차이는 PET 을이용한연구에서는양측반구의혈류변화를정량적으로분석한것에비하여본연구는상대적인비율만을비교한방법의차이때문이라고생각한다. 실제로 PET 연구에서스텐트를삽입한쪽의뇌혈액량 (cerebral blood volume, ml/100 g) 의평균값은시술전 3.45±0.69, 시술 1개월째 3.48±0.75, 시술 6개월째 3.41±0.53 이었으며반대쪽의경우각각 3.63±0.72, 3.66±0.66, 3.30±0.46 이었다. 이를본연구에서 Pre-ACZ- SPECT GCR 을구한것처럼스텐트삽입술을시행하지않은쪽에대한스텐트삽입술을시행한쪽의비율로다시계산하면 , , 으로본연구의결과 ( 편측협착군 : 0.972±0.048, 0.973±0.056, 0.978±0.065, 증상군 : 1.001±0.118, 1.021±0.188, 1.034±0.201) 와같이시기에따라증가한다. 따라서스텐트삽입술후초기에는증가하다가시간이지나며감소하는경향을보인본연구의뇌혈관반응도역시실제적으로는시간이지나며호전되지만연구방법의차이때문에나타난현상일가능성이크다고생각한다. 흥미롭게도양측협착군에서는편측협착군에비해시간이흐를수록뇌혈관반응도가악화되었는데 (Table 2) 이는사용한공식때문이다. 양측협착군의경우스텐트삽입술을시행한측의경동맥을통해양측대뇌반구에뇌혈류를공급하게되면서스텐트시술측과반대측모두에서 Pre- 와 Post-ACZ-SPECT 의 GCR 이증가하였다. 이는스텐트삽입술을시행한측의혈류가반대편에비해상대적으로더많이증가하기때문에나타나는현상으로실제로뇌혈관반응도는호전되나본연구에서뇌 혈관반응도를구한공식 (CVR=GCR of pre-acz-spect - GCR of post-acz-spect) 의정의때문에악화되는것처럼보인다. 따라서 SPECT 결과분석에있어서반대측경동맥의협착상태에대한고려가필요하다. 또한스텐트삽입술전뇌혈관반응도가음의수치를나타내어뇌혈관예비능이좋다고판단하였던편측협착군환자 5명중 4명과증상군환자 2명모두에서시기에따라뇌혈관반응도는오히려감소하는것으로나타났다. 이역시정상적인뇌혈관자동조절능이증가된혈류량에대해적절한반응을보임에따라값이적어지는결과를보인것이다. 본연구의가장큰제한점은정량분석의방법으로전체대뇌반구를대상으로하여뇌지도분석법 (statistical parametric mapping; SPM) 을사용하지않고 5 mm 두께의횡단세개에서관심영역을설정한후그영역의감마값을비교한것이다. 내경동맥의혈류는전두- 두정엽피질, 등가쪽 (dorsolateral) 전두엽, 그리고측두엽앞위쪽 (anterosuperior) 에서가장잘반영된다는점이알려져있으나 28 기술적인문제로이부분의혈류변화를측정하지못하였다. 대상횡단면을선택하는과정이나관심영역을설정하는과정에서도검사자의주관이개입될여지가크며 SPECT 촬영과정에서각대상마다촬영시간차가감마계수에영향을줄수있다. 또한여러연구에서수술 / 시술후반대측의뇌혈류량역시시술측의증가량보다는적은범위이기는하나곁순환의영향에의해증가하는것이밝혀졌기때문에양쪽대뇌반구의혈류량증가정도를절대값은무시한채단순히양쪽반구사이의상대적인비율만을비교하는것이결과를왜곡하였을가능성이있다. 8,27 마지막으로연구에포함된환자의수가적다는점역시통계분석이나연구결과의적용에제한점으로작용한다. 결론적으로경동맥협착에의해손상된뇌혈관자동조절능은스텐트삽입술후다시회복된다. 이러한변화는반대편경동맥에심한협착이나폐쇄가없는환자군에서나증상경동맥협착환자군에서더뚜렷하다. 이러한결과를재확인하기위해다수의환자를대상으로객관적인정량적분석법을이용한장기간의연구가필요하다. REFERENCES 1. Goldstein LB, Adams R, Alberts MJ, Appel LJ, Brass LM, Bushnell CD, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research J Korean Neurol Assoc Volume 29 No. 4,

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