ORIGINAL ARTICLE online ML Comm J Neurocrit Care 2009;2:44-49 ISSN 2005-0348 두개내외뇌동맥스텐트삽입술후확산강조영상에서새롭게발견된뇌허혈병변의빈도와특성 CHA 의과학대학교신경과학교실, 1 방사선과학교실, 2 한양대학교의과대학방사선과학교실 3 김미화 1 김상흠 2 이영준 3 오승헌 1 김현숙 1 김원찬 1 김옥준 1 Frequency and Characteristics of Newly Detected Cerebral Ischemic Lesions on Diffusion-Weighted Imaging after Stent Insertion of Intra- or Extracranial Cerebral Arteries Mi-Hwa Kim, MD 1, Sang Heum Kim, MD 2, Young-Joon Lee, MD 3, Seung-Hun Oh, MD 1, Hyun Sook Kim, MD 1, Won-Chan Kim, MD 1 and Ok Joon Kim, MD, PhD 1 1 Departments of Neurology, 2 Radiology, CHA University School of Medicine, Seongnam, Korea 3 Department of Radiology, Hanyang University College of Medicine, Seoul, Korea Background: Small emboli arising from a friable plaque during intra-arterial procedure lead to cerebral ischemic lesion (CIL) in some patients with cerebral arterial stenosis. We investigate the frequency and characteristics of symptomatic or asymptomatic CIL after stent insertion in cerebral arterial stenosis. Methods: This study enrolled consecutive 40 patients who performed stent insertion for treatment of significant intra- and extra-cranial arterial stenosis. We compared serial diffusion-weighted imaging (DWI) of brain before and within 48 hours after intervention to detect newly developed CIL. The neurological deterioration was checked at the same time. Results: Twenty-seven of total 40 cases (67.5%) had newly developed CIL on follow-up DWI scan. Most CIL were multiple and dot-shaped lesions scattered in peripheries of intracranial arteries. Thirteen patients (48.1%) developed CIL at relevant arterial territory of procedure and the rest (51.9%) developed at combined relevant and irrelevant vascular territory or irrelevant vascular territory only. Most of cases with CIL (85%) were asymptomatic on follow-up neurological exam. In 4 symptomatic cases, three cases showed transient ischemic symptoms and one showed severe neurological deterioration. On comparison of risk factors between CIL-positive and CIL-negative groups, no differences in age, sex, vascular risk factors, operator and procedure time were found. Conclusion: The frequency of newly developed CIL after stent procedure is relatively high and most CIL were asymptomatic. However, in some case, neurological deterioration can occur. So then, to decrease CIL in stent procedure, intensive preventive therapy will be needed. Also, it is important to monitor the clinical symptoms carefully, and to use sufficient anticoagulation before and after stent procedure. J Neurocrit Care 2009;2:44-49 KEY WORDS: Stenosis Stent insertion Diffusion-weighted image Infarction. 서 심한뇌혈관의협착을치료하는방법으로내경동맥박리술 (carotid endarterectomy: CEA), 경피적풍선혈관성형술 (percutaneous transluminal balloon angioplasty: Address for correspondence: Ok Joon Kim, MD, PhD Department of Neurology, CHA University School of Medicine, Bundang CHA Medical Center, 351 Yatap-dong, Bundang-gu, Seongnam 463-712, Korea Tel: +82-31-780-5480, Fax: +82-31-780-5269 E-mail: okjun77@cha.ac.kr, okjun77@hanmail.net 론 PTA) 및스텐트 (stent) 삽입술이있다. 최근뇌졸중을치료혹은예방하고자하는노력으로대뇌혈관에심한협착이있는환자에서혈관을넓혀혈류를개선시키는스텐트삽입술의이용이점차증가하고있다. 이전스텐트삽입술은 CEA의고위험환자에서대체치료로써사용되어왔으나최근여러연구에서스텐트삽입술은 CEA와대등한치료효과를가지고있음이보고되고있다. 1-5 그러나스텐트삽입술또한침습적인시술중의하나로시술중혈관파열또는박리, 혈전에의한급성혈관폐색 44 Copyright c 2009 The Korean Neurocritical Care Society
Cerebral Ischemic Lesions after Stent Insertion MH Kim, et al. (obstruction), 색전에의한원위부경색등의합병증발생위험이있으며시술후신경학적결손이 5~9% 정도에서발생한다. 6 최근진단방사선학적기술의발달로확산강조영상 (diffusion-weighted image: DWI) 이급성기뇌경색을발견하는데많은도움이되고있는데 7,8 스텐트삽입술후 DWI 검사를이용하여시술후뇌허혈병변 (cerebral ischemic lesion: CIL) 의빈도를조사한연구들을보면신경학적손상이나타나지않더라도영상검사에서 CIL이높은비율로발생한다고보고하고있다. 6,9-12 저자들은두개내혹은두개외혈관에협착이발견되어스텐트삽입술후, DWI 검사에서새로이발견된증상성혹은무증상성 CIL의빈도및특성과위험인자를분석하고자하였다. 대상및방법 2006년 6월부터 2008년 12월까지분당차병원신경과에서뇌혈관협착이발견되어스텐트삽입술을시행한환자중삽입술전후두차례 DWI 검사를시행하였던환자 40명을대상으로하였다. 남자는 29명 (72.5%), 여자는 11명 (27.5%) 이었으며평균연령은 65.4세 (38~87세) 였다. 일과성뇌허혈발작 (transient ischemic attack: TIA) 이나뇌경색으로온환자가 28명 (70%) 이었고, 뇌경색과거력이나신경학적결손의증상이없는 70% 이상의무증상성혈관협착이있는환자는 12명 (30%) 이었다 (Table 1). TIA 환자는증상발생후최소 48시간이경과한후시술을하였고, 뇌경색환자는응급스텐트삽입술이시행된경우를포함하여모두한달이내에시술을받았다. 혈관의협착부위는내경동맥협착 31명 (77.5%), 중대뇌동맥협착 1명 (2.5%), 외경동맥협착 1명 (2.5%), 추골동맥협착 6명 (15%), 뇌기저동맥협착 1명 (2.5%) 이었다 (Table 1). 대부분최소한스텐트삽입술 4일전부터 aspirin 100~ 200 mg과 clopidogrel 75 mg을전처치하였으나, 응급스텐트삽입술을시행한경우 aspirin 200~300 mg, clopidogrel 300 mg을고용량투여하였다. 모든환자에서시술시 3,000 unit의헤파린을단회정맥내로전량 (bolus) 투여하였고, 대퇴동맥을통해양측경동맥과추골동맥의진단적뇌혈관조영술을먼저시행하여협착의정도를측정하였다. 24명의환자는진단적혈관조영술직후스텐트삽입술을시행받았고, 16명의환자는진단적혈관조영술후 1~ 7일이내스텐트삽입술을시행받았다. 스텐트삽입술은먼저유도카테터 (guiding catheter) 를병변쪽혈관에위치시킨후스텐트를삽입한후확장시켜장착하였다. 스텐트 TABLE 1. Demographical characteristics of patients and location of stent insertion N (%) Sex (M : F) 29/11 (72.5/27.5) Age (yrs) 65.4±9.77 Type of vascular event Symptomatic 28 (70.0) Stroke 23 (57.5) TIA 05 (12.5) Asymptomatic 12 (30.0) Vascular risk factor Hypertension 29 (72.5) Diabetes mellitus 18 (45.0) Smoker 20 (50.0) Hyperlipidemia 09 (22.5) Previous stroke 14 (35.0) Cardiac disease* 07 (17.5) Location of stent insertion Proximal ICA 21 (52.5) Proximal ECA 01 (02.5) Distal ICA 10 (25.0) MCA 01 (02.5) Basilar artery 01 (02.5) Proximal vertebral artery 06 (15.0) Total 40 (100) *atrial fibrillation, valvular heart disease, coronary artery obstructive disease. M: male, F: female, TIA: transient ischemic attack, ICA: internal carotid artery, ECA: external carotid artery, MCA: middle cerebral artery 의통과가어려웠던 25명의경우삽입전협착된부위에먼저 PTA를시행하여혈관내경이충분히확보된후스텐트를장착하였다. 과정중에스텐트가충분히펼쳐지지않은경우스텐트삽입후 PTA를다시시행하였다. 스텐트삽입이완료된 20분후혈관조영술을다시시행하여시술중혈관폐색이나수축, 박리등의발생유무를확인하였다. 내경동맥스텐트삽입술시 3명의환자에서원위부보호기구 (protection device: AngioGuard TM Emolic Capture, Cordis corporation, Miami, FL, USA) 가사용되었다. 스텐트는 Precise stent(cordis, Roden, Netherlands), Flexmaster stent(abbott Vascular, JoMed. GmbH, Rangendingen, Germany), Xpert stent(abbott Vascular, Santa Clara, CA, USA) 및 Wallstent(Boston Scientific Ltd, Natick, MA, USA) 네종류의스텐트를지름 2.5~8 mm, 길이 9~40 mm까지혈관부위와협착정도에따라시술자가선택하여사용하였다. 시술시간은평균 80.7분 (40~ 120분 ) 이었다. 5년이상스텐트삽입술에경험이있는영상의학과전문의 2명이각각 25명, 15명을시술하였다. 환자의임상증상악화는시술후 48시간이내 National 45
J Neurocrit Care 2009;2:44-49 Institute of Health Stroke Scale(NIHSS) 점수가 2점이상악화되었을경우로정의하였다. 신경학적결손이외시술후 48시간이내 TIA 증상유무, 어지럼증 (dizziness), 두통 (headache), 오심및구토등의전신증상이있는지의여부와시술부위의출혈, 혈종 (hematoma) 의생성및전신출혈의빈도를분석하였다. 모든환자는두차례 DWI를시행하였고시술전최대 30 일이내, 시술후에는 48시간이내에시행하였다. 두명의신경과전문의와한명의영상의학과전문의가시술전에는보이지않던 CIL이시술후 DWI 검사에서고신호강도로보이고겉보기확산계수영상 (afferent diffusion coefficiency: ADC) 에서저신호강도를보이면시술후발생한새로운병소로규정하여개수및위치를분석하였다. 시술전환자의위험인자, 시술시간등의요인을분석하기위하여 CIL 양성군과 CIL 음성군으로나누어, 비연속성독립변수는 Fisherʼs exact test, 연속성독립변수는 Mann-Whitney U test를 SPSS ver. 12.0(Microsoft Corp., Chicago, IL, USA) 을사용하여분석하였다. TABLE 2. Frequency and topographic findings of 27 patients with diffusion weighted image-positive lesion after stent insertion N (%) Presence of neurological deficits Symptomatic 04 (14.8) Stroke 01 (03.7) TIA 03 (11.1) Asymptomatic 23 (85.2) Distribution Ipsilateral 16 (59.3) Bilateral 11 (41.7) Number of DWI-positive lesion Single lesion 09 (33.3) Between two and three lesion 05 (18.5) More than three lesion 13 (48.2) Vascular topography of DWI-positive lesion Relevant arterial territory 13 (48.1) Irrelevant arterial territory 04 (14.8) Relevant and irrelevant arterial territory 10 (37.1) DWI: diffusion weighted image A B C 결 과 스텐트삽입술을시행한총 40명의환자중시술후 48 시간이내 DWI에서새로운 CIL이발견된환자는 27명 (67.5%) 이었다. 이중 23명 (85.2%) 에서는신경학적증상의변화가없었으며 3명의환자는시술중후 TIA 증상을보였고나머지 1명에서는시술 18시간후에기존의신경학적결손이악화되었다 (Table 2). 시술중 TIA 증상을보인 3명중한명은기저동맥시술후마비성구어장애 (dysarthria) 를다른한명은우측내경동맥시술시좌측상하지위약을보여시술혈관에합당한 TIA 증상을보였고, 다른한명은우측원위부내경동맥시술후우측감각저하및저린감을호소하였는데 DWI에양측으로다발성병변이관찰되었다. 악화된 1명의환자의경우좌측후두엽, 좌측뇌간, 우측뇌량팽대부위및양측소뇌뇌경색을보여기저동맥상부폐쇄증후군양상이관찰되었다. 뇌자기공명영상혈관조영술 (magnetic resonance angiography: MRA) 상후뇌순환 (posterior circulation) 에해당하는혈관들이거의보이지않았고우측내경동맥에서심한협착과좌측내경동맥에서중등도의협착이관찰되었다. 혈관조영술에서우측추골동맥의폐색, 좌측원위부추골동맥및기저동맥의느린혈류속도및좌측내경동맥의 50% 가량의협착이관찰되었고우측내경동맥에서 90% 이상의협착이관찰되었 FIGURE 1. Preoperative (A) and postoperative (B) diffusion-weighted images and preoperative magnetic resonance angiography (C) of one symptomatic case. Severe stenosis of proximal portion of right internal carotid artery and moderate stenosis of distal portion of left internal carotid artery is noted (arrow, R: right). 다. 내경동맥에서후뇌순환으로혈류공급이이루어지는소견이관찰되어우측내경동맥에스텐트삽입술을시행하였다. 환자는스텐트삽입술후 18시간뒤의식저하가발생하였고 NIHSS 점수가시술전 8점에서시술후 17점으로악화되었다. 시술후시행한 DWI 검사상기존의뇌경색부위외우측후두엽, 우측뇌간부위및좌측측두엽뇌경색이관찰되었다 (Fig. 1). 가역적인신경학적증상을보인 3 명과무증상의 23명의환자에서관찰된 CIL은주로뇌피질과백질경계부위혹은백질부위에서직경 15 mm 이하 46
Cerebral Ischemic Lesions after Stent Insertion MH Kim, et al. 의점 (dot) 형태의경색이었다. 한쪽대뇌반구에서발생한경우는 16명 (59.3%), 양측대뇌반구에서병변이관찰된경우는 11명 (41.7%) 이었다. 총 9명 (33.3%) 의환자에서 1개의 CIL만관찰되었고 2~3개가 5명 (18.5%), 3개이상의병변을보인경우는 13명 (48.2%) 이었다 (Table 2). 앞뇌순환영역혈관 ( 내경동맥, 중대뇌동맥및외경동맥 ) 에시술을받은 33명중 22명 (66.7%) 에서 CIL이발생하였고이중 10명 (45.5%) 이시술관련혈관영역에만병변이관찰되었고 9명 (40.9%) 은시술부위혈관영역및다른혈관영역에서함께병변이관찰되었다. 시술혈관과관련이없는영역에만 CIL이생긴경우는 3명 (13.6%) 이었다. 후뇌순환영역혈관 ( 추골동맥및뇌기저부동맥 ) 협착으로시술받은 7명중 5명 (71.4%) 에서 CIL이발생하였고이중 3명 (60%) 의환자가시술관련혈관영역에서 1개의병변을보였고한명은양측성으로 2개씩나머지한명은앞뇌순환영역에만 CIL이발생하였다 (Table 3). 시술전증상유무, 시술위치, 스텐트삽입전 PTA 유무및시술자간의차이는발견되지 않았다 (Table 3). CIL 양성군과 CIL 음성군에서환자의나이, 뇌졸중위험인자및시술시간도통계학적으로차이를보이지않았다 (Table 4). 시술중혈압, 심박수가감소하여 atropine 을정주한경우가 5명이었고혈뇨를보인경우, 시술부위혈종을보인경우가각각 1명이었으나시술 7일이내에모두호전되었다. 시술후어지럼이나두통을호소한환자는없었다. 고찰 Bendzus 등 13) 이처음으로뇌혈관조영술검사를받은 100 명의환자중 23명에서검사후신경학적변화없이 DWI 영상에서고신호강도가보였다고보고한이후뇌혈관조영술, 혈관성형술및스텐트삽입등중재적뇌혈관시술후임상적증상이없어도 DWI 영상에서고신호강도를보이는 CIL이발생할수있다고보고되고있다. 이전연구에서중대뇌동맥과경동맥의스텐트삽입술시행후대개 20~ 30% 환자에서신경학적변화없이시술후새로운 CIL이 TABLE 3. Analysis of potential risk factors of positive cerebral ischemic lesion on diffusion weighted-image Risk factors N (40) CIL-positive (n=27) CIL-negative (n=13) P-value Type of vascular event Symptomatic (TIA or stroke) 28 20 (71.4%) 08 (28.6%) 1.00 Asymptomatic 12 07 (58.3%) 05 (41.7%) Location of stent insertion Anterior circulation* 33 22 (66.7%) 11 (33.3%) 1.00 Posterior circulation 07 05 (71.4%) 02 (28.6%) PrePTA Yes 25 16 (64.0%) 09 (36.0%) 0.73 No 15 11 (73.3%) 04 (26.7%) Operator Operator 1 25 17 (68.0%) 08 (32.0%) 1.00 Operator 2 15 10 (66.6%) 05 (33.4%) *anterior circulation including ICA, ECA and MCA and posterior circulation including VA and basilar artery. PTA: percutaneous transluminal balloon angioplasty, CIL: cerebral ischemic lesion TABLE 4. Comparison of demographical and procedural factors between cerebral ischemic lesion-positive and negative group after stent insertion Risk factors CIL-positive (n=27) CIL-negative (n=13) P-value Age (yrs)* 65.4±10.8 65.4±7.51 0.99 Sex (M : F) 18 : 9 10 : 3 1.00 Hypertension 19 (70.4%) 10 (76.9%) 1.00 Diabetes mellitus 12 (44.4%) 06 (46.2%) 1.00 Smoker 13 (48.1%) 07 (53.8%) 1.00 Hyperlipidemia 07 (25.9%) 02 (15.4%) 0.69 Previous stroke 10 (37.0%) 04 (30.8%) 1.00 Cardiac disease 05 (18.5%) 02 (15.4%) 1.00 Procedure time (min)* 81.5±21.1 76.1±24.4 0.13 *mann Whitney U test 47
J Neurocrit Care 2009;2:44-49 나타났음을보고하였다. 3,10,12-19 본연구에서스텐트삽입술후새로이발생한 CIL의빈도는 67.5% 로이전연구들에비해높은편이었으나 70% 까지보고된경우도있어 11 외국연구와본연구의결과를종합적으로고려하면비록임상적증상이없더라도스텐트삽입술후발생하는무증상 CIL의빈도는대체적으로높다고생각된다. 다만대다수의이전외국연구들보다높은결과를보인것은이전연구들에비해색전발생의위험이높은 3주이내스텐트삽입술을시행한경우가포함된것이원인일수있다. 20 본연구에서는 48.1% 의환자만이시술과관련된혈관 (relevant artery) 측의뇌영역에서병변을보였고, 51.9% 의환자에서는양측성및시술과관련되지않은곳에서새로운병변이발견되어혈전이시술과관련되지않은혈관의영역이나반대측혈관으로도전파되는빈도가높음을알수있었다. 여러연구에서 9~31% 의환자에서시술부위혈관이외의영역에서새로운병변이발견됨을보고하고있다. 9,10,14,21 본연구에서도약 52% 의환자가시술부위혈관이외의영역에서새로운 CIL이발견되었고이전연구결과에비해높은빈도를보였다. 확실한원인은알수없으나제시된몇몇기전들을보면첫째, 협착부위에서발생한혈전이원위부로이동하여윌리스환 (circle of Willies) 를통한측부순환으로반대편이나다른혈관영역으로이동하였을가능성이있고, 둘째, 가이드와이어 (guide wire) 를조작할때대동맥궁 (aortic arch) 에서생긴파편들이다른혈관영역으로전파되었을가능성도있으며, 9-11,14 또한스텐트삽입술에의한혈액응고계의활성에의한혈전생성촉진도가능성이있다. 이러한점은혈류역동학적인자도고려함과동시에스텐트삽입술시에시술과관련된물리학적인기술적인인자또한배제될수없다는것을시사하므로시술시가이드와이어등을안전하게다루는것도매우중요하다고볼수있다. McDonnell 등 22 은스텐트삽입술후증상성뇌경색이발생한경우는 7.2% 로이중심각한후유증을남기는뇌경색 (disabling stroke) 과사망률의빈도는 1.8% 로보고하였다. 본연구에서는증상성뇌경색이발생한경우는 1명 (2.5%) 이었는데환자의경우시술전부터관찰되었던후뇌순환의저류가악화되었거나후뇌순환의저류를앞뇌순환의보상기전으로혈액을추가로공급되던중경동맥스텐트삽입술을하면서후뇌순환쪽으로혈전등이떨어져나갔을가능성도생각해볼수있겠다. 시술후생기는 CIL의빈도가시술시간, 나이, 뇌졸중이나 TIA, 혈관염, 다발협착과혈관협착의길이등의요인 들과관련이있다는보고가있으며 2,13,23 실험실연구에서무반향성의플라크 (echolucent plaque) 와 90% 이상의 stenosis를동반한플라크가색전발생가능성이높다는연구도있다. 24 다른연구들에서는시술전신경학적이상의정도, 혈관위험인자 ( 고혈압, 당뇨, 고지혈증, 흡연, 심장병, 말초혈관질환 ), 스텐트종류및협착정도등과새로운 CIL 의발생은관련이없다고보고하였다. 15,21 본연구에서는나이, 시술시간, 시술자, 혈관위험인자와 CIL의발생과는유의한차이를발견할수없었다. 그러나본연구에서포함된환자의수가적고이로인해혈관영역별분석을하지못한제한점으로차이를발견할수없을가능성도있어시술후 CIL의발생에영향을미치는인자에대한연구는추후많은환자를대상으로한후속연구가필요할것으로생각한다. 통계적으로유의하지는않았으나증상성환자의경우무증상에비해 CIL의발생률이높고 (71.4%, 58.3%) 시술중후 TIA나뇌경색이발생한 4명중 3명이뇌경색으로온경우로증상성환자가시술중후부작용위험이높음을확인할수있었다. 경동맥스텐트삽입시원위부보호기구를사용하면임상적그리고무증상 CIL을감소시킨다는연구결과들이있다. McDonnell 등 22 의연구에서원위부보호기구를설치한그룹과설치하지않은그룹에서증상성 CIL은각각 5%, 25% 였고 DWI에서발견된무증상 CIL은각각 18%, 33% 로원위부보호기구의 CIL 발생의보호효과를보고하였다. 또한 Andreas 등도원위부보호기구를사용한후 DWI에서발견된병변이 67% 에서 49% 로, 뇌경색과사망률이 7.5% 에서 4.3% 로감소함을보고하였다. 25 그러므로스텐트삽입술시향후원위부보호기구를사용하는것이무증상 CIL의발생을줄이는데도움이된다고생각된다. 본연구에서는내경동맥스텐트삽입술을시행한 31명의환자중 3명에서보호기구를사용하였고이중 2명에서 CIL이발견되었다. 보호기구를사용한환자들에서 CIL이더발생하였으나환자수가적어분석및의미를찾기에는부족하다고생각되며앞으로보다많은환자들을대상으로한분석이필요하겠다. 결론적으로본연구에서스텐트삽입술후발생한대부분의 CIL은무증상 CIL로환자의예후에는영향을미치는수준은아니었다. 스텐트삽입술은비교적안전한시술법으로생각할수도있으나, 최근연구에서무증상 CIL은인지기능의감소나병변이반복적으로발생했을때혈관성치매의위험도를높이는것으로알려져있다. 26 따라서시술전, 후인지기능의세밀한변화를조사할필요가있으며시술전환자및보호자에게무증상 CIL의발생가능성을사전에주지시키고적절한항응고제혹은항혈소판제제 48
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