Original Article pissn 1738-2637 / eissn 2288-2928 J Korean Soc Radiol 2016;75(5):346-353 http://dx.doi.org/10.3348/jksr.2016.75.5.346 Clinical Experience of Intra-Arterial Therapy in Patients with Acute Ischemic Stroke from a Single Institute So Young Park, MD 1, Hanbin Lee, MD 2, Jonguk Kim, MD 2, Seung Hun Oh, MD 2, Jinkwon Kim, MD 2, Nam Keun Kim, PhD 3, Sang Heum Kim, MD 4, Ok Joon Kim, MD 2 * 1 Department of Neurology, Seoul National University-Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea Departments of 2 Neurology, 4 Radiology, CHA Bundang Medical Center, CHA University, Seongnam, Korea 3 Institute for Clinical Research, School of Medicine, CHA University, Seongnam, Korea Purpose: To compare the efficacy and safety between intra-arterial therapy (IAT) and intra-venous and intra-arterial combined therapy (IVIACT) in patients with acute ischemic stroke in the anterior circulation territory. Materials and Methods: Forty-one patients treated with IAT using Solitaire were retrospectively reviewed. Nineteen patients were treated with IAT, twenty-two patients were treated with IVIACT, and ten patients of the forty-one patients were managed with multimodal treatment like stent, balloon angioplasty etc. We investigated the rate of recanalization and hemorrhage, NIH stroke scale and 3-month modified Rankin Scale. Results: The overall recanalization rate was 93% and symptomatic ICH occurred in 10% of the patients. There was no difference in hemorrhage, recanalization rate, and early improvement between IAT and IVIACT. Good outcome was more frequently observed in 59% of the patients with IVIACT than 36% of the patients treated with IAT without any significant difference. The patients managed with multimodal treatment did not show any significant hemorrhage outcome. Conclusion: IAT using Solitaire is a useful treatment method without high risk in patients with acute ischemic stroke in the anterior circulation territory. Also, IVIACT and multimodal treatment might be considered as reasonable therapeutic options in these patients. Index terms Stroke Mechanical Thrombolysis Tissue Plasminogen Activator Received February 16, 2016 Revised April 5, 2016 Accepted May 26, 2016 *Corresponding author: Ok Joon Kim, MD Department of Neurology, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Korea. Tel. 82-31-780-5481 Fax. 82-31-780-5269 E-mail: okjun77@cha.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 서론 급성허혈성뇌졸중발생시혈류를재개통시키는혈전용해술은매우효과적인치료법이다 (1, 2). 다만, 재조합플라스미노겐활성제 (recombinant tissue plasminogen activator; 이하 rtpa) 를정맥내로투여하는정맥내혈전용해술의경우뇌경색발생후 4.5시간이내에서만안전성과효과가입증된상태이기에임상적으로적응증이되는환자군이제한적이다. 또한정맥내혈전용해술을시행하더라도실질적인혈관의재개통성공률에도한계가있다 (3). 이러한정맥내혈전용해술의한계를극복하기위한접근법으로혈관내치료가있다. 혈관내치료는막힌동맥혈관에카테터를접근시켜직접혈전용해제를투여하거나 The Mechanical Embolus Removal in Cerebral Ischemia ( 이하 MERCI), Penumbra system, Solitaire, Trevo 등을이용하여혈전을물리적으로제거하는방식이다. 정맥내혈전용해술의적응증이되지않는경우나시행후에도재관류에실패한경우혈관내치료가대안적치료법으로제시될수있다. 현재많은 3차진료급병원에서혈관내치료를처음부터시행하거나정맥내혈전용해술이실패한경우이어서혈관내치료를시행하고있다. 혈관내치료는정맥내혈전용해술에비해시간이더오래걸리고시술을위한제반시설과숙련된의료진이필요하다는제한점이존재한다. 이러한제한점으로인하여표준치료법으로인정되기위한대규모임상연구가쉽지않아정맥내혈전용해술에비해혈관내치료는상대적으로근거가충분하지못하였으나, 그 346 Copyrights 2016 The Korean Society of Radiology
박소영외 동안시행된여러연구와경험이축적되면서혈관내치료의임상적유용성과효과들이널리인정받고있다 (4-6). 특히최근의임상연구결과들에서는 Solitaire 와같은스텐트를통한혈전제거술의경우, 기존의약물을통한동맥내혈전용해술에비하여상대적으로높은재관류율과장기적예후향상효과를보였다. 본연구에서는단일대학병원에서전순환부위의급성허혈성뇌졸중환자를대상으로 Solitaire 를통한혈관내치료의결과를분석하고자한다. 또한혈관내치료만시행한경우와정맥내혈전용해술에이어서혈관내치료를함께시행한환자사이에안전성과효용성을비교해보고병용요법 (multimodal treatment) 의유용성에대한평가도아울러시행하고자한다. 대상과방법 대상환자 2011년 10 월부터 2014 년 7월까지입원한급성뇌경색환자중 1) 내원당시시행한컴퓨터단층촬영혈관조영술 (CT angiography) 에서중간대뇌동맥또는내경동맥의폐색이관찰된환자, 2) 증상발생후 10 시간이내에 Solitaire 를이용한혈관내치료를시행한환자 41 명을후향적으로조사하였다. 본연구는차의과대학차병원의임상시험심사위원회 (Institutional Review Board; 이하 IRB) 의심의후허가를받았다. Solitaire 를사용하지않은경우및혈관내치료후 24 시간이내조기전원으로경과를확인할수없는경우는본연구대상에서제외되었다. 상기기준에따라선정된 41 명의대상환자중 19 명은정맥내혈전용해술없이혈관내치료를시행한환자군 (intra-arterial therapy; 이하 IAT) 이고, 나머지 22 명의환자는정맥내혈전용해술이후에혈관내치료를연이어시행한환자군 (intravenous and intraarterial combined therapy; 이하 IVIACT) 으로분류하였다. 정맥내혈전용해술과혈관내치료의시술방법정맥내혈전용해술은뇌졸중학회진료지침및 European Cooperative Acute Stroke Study ( 이하 ECASS) III trial results 의적응증에근거하여뇌경색증상발생 4.5시간내에 tpa 를주사하였다 (7, 8). tpa 용량은몸무게 kilogram 당 0.9 mg으로계산하여 10% 는 bolus 로주사하고나머지 90% 는한시간동안정주하였다. 혈관내치료는 Solitaire revascularization device (Covidien, Irvine, CA, USA) 를이용한기계적혈전제거술의방법으로시행되었다. 혈관내치료를시행하는경우혈전의위치확인을위하여대퇴동맥을통한진단적혈관조영술을같이시행하였다. 혈관내치료시우선 6 Fr sheath (Codman, Raynham, MA, USA) 를내경동맥의목부분 (cervical portion) 에위치시켰으며, 미세도관 (Cordis Corp., Bridgewater, NJ, USA) 을혈전의원위부에접근시켰다. 이후미세도관을통하여 Solitaire 가혈전의위치전부를덮도록삽입하였다. Solitaire 가제대로위치하였는지내경동맥혈관조영술을통해확인하였으며 2~5분정도뒤에천천히 Solitaire 를당겨혈전의제거를시도하였다. 혈전제거시에는혈전이다시떨어져나가는재색전을방지하기위해 40 cc 주사기를이용한지속적인음압을가하였다. 모든환자는두개강내출혈의여부등을확인하기위해시술 24 시간에뇌 CT를시행하였고혈액관류상태및뇌경색정도를확인하기위해 48 시간내에 diffusion MRI 및 MR angiography 를시행하였다. 혈관내치료시필요에따라추가적으로 GPIIb/GPIIIa 길항제인 tirofiban 을동맥내투여하거나 (9), 풍선혈관성형술 (balloon angioplasty) 및스텐트삽입과같은기구를이용한방법을다각도로병용하여사용하기도하였다. 자료수집혈관질환의위험인자는 1) 고혈압 : 이전에진단받은병력이있거나약물투여중인경우, 2) 당뇨병 : 혈당강하제를투여한병력이있거나입원이후회복기에시행한공복혈당이 126 mg/dl 이상또는식후 2시간째혈당이 200 mg/dl 이상인경우, 3) 심혈관질환 : 심인성뇌졸중의고위험인자 (high risk) 로분류된질환을가진경우 (10), 4) 고지혈증 : 과거진단병력이있거나고지혈증약물을복용중인경우, 혹은입원후시행한공복검사상에서저밀도콜레스테롤 160 mg/dl 또는총콜레스테롤 240 mg/dl로확인된경우, 5) 뇌졸중의과거력 : 뇌영상검사상과거병변이확인되었거나이전에뇌졸중으로진단받은경우로정의하였다. 혈관내치료를시행한환자의치료후평가로서시술이끝난뒤 1시간째 National Institutes of Health Stroke Scale ( 이하 NI- HSS) 점수, 3개월후 modified Rankin Scale ( 수정 Rankin 척도 ) 를이용하였다. 혈관내치료시행후 NIHSS 점수가내원당시의 baseline NIHSS 에비해서 50% 이상의감소를보인경우를초기신경학적호전 (early neurologic improvement) 으로정의하였다. 수정 Rankin 척도는 0 = 증상이없는상태, 1 = 증상은있으나유의한장애가없는경우, 일상생활영위할수있는상태, 2 = 다소장애가있어이전활동을완전히할수없는상태, 하지만도움없이자기일은돌볼수있는상태, 3 = 일상생활에도움이필요하나독립적으로보행은가능한경우, 4 = 중등도또는심한장애가있는상태, 도움없이는보행불가하고본인의신체적욕구를충족시킬수없음, 5 = 심한장애, 누워서지내고있고실금이있으면서지속적인간호가필요한상태, 6 = 사망으 jksronline.org 대한영상의학회지 2016;75(5):346-353 347
로평가된다 (11). 뇌졸중발병후기능예후평가로서 3개월후수정 Rankin 척도가 0~2점은좋은예후 (good outcome) 로, 3~6점은나쁜예후 (bad outcome) 로분류하였다. 혈관의재개통에대한평가는 Thrombolysis in Cerebral Ischemia ( 이하 TICI) 점수로분류하였고시술후성공적인재개통은 TICI 점수가 2b 이상인경우로정의하였다 (12). 혈관의재개통정도는최종적인혈관조영술시행후 1명의신경중재전문의와 1명의신경과전문의에의해평가되었다. 혈관내치료이후뇌출혈의발생은 ECASS 에서제시한방사선적소견에근거하여출혈성뇌경색 (hemorrhagic infarction) 과실질성출혈 (parenchymal hemorrhage) 로분류하였다 (2). 그리고뇌영상으로입증된뇌출혈이 NIHSS 점수에서 4점이상의신경학적악화와연관되었을것으로판단된경우를증상성뇌출혈로정의하였으며이외의경우는무증상성뇌출혈로구분하였다 (13). 분석 IAT 환자군과 IVIACT 환자군간의시술후혈관의재개통의성공유무, NIHSS 점수, 뇌출혈의발생, 발병후 3개월째수정 Rankin 척도에대해서비교분석하였다. 두그룹간비교에있어서나이, 발병후시술까지걸린시간, NIHSS, 수정 Rankin 척도와같은연속변수는 Mann-Whitney U test 를이용하였고, 성별, 기저질환유무, 재개통여부와뇌출혈여부와같은비연속변수는 Fisher s exact test 를이용하였다. 통계적유의성은 p값이 0.05 이하인경우로정하였다. 결과 시행한총 41 명의환자중남성은 28 명 (68%), 여성은 13 명 (32%) 이었고, 평균연령은 64.7세였다 (Table 1). 증상발생시점부터최초재관류치료시작까지의시간은평균 3.4시간이며입원당시 NIHSS 점수는평균 12 점이었다. 폐색혈관은각각내경동맥이 18 명, 중대뇌동맥이 23 명이었다. 총 41 명중, IAT 환자군은 19 명 (46.3%) 이었고나머지 22 명 (53.7%) 은 IVIACT 를시행하였다 (Table 2). 두환자군의임상적소견을비교하면내원시 NIHSS 점수는각각 12, 13 점으로유의한차이를보이지않았다 (p = 0.36). 위험요인의빈도에서는 IAT 환자군에서뇌졸중과거력이유의하게높은소견을보이지만 (p = 0.01) 그외, 명시된위험요인은두환자군간에통계적으로의미있는차이를보이지않았다. 전체 41명의환자가운데시술후재개통에성공한경우는 93%(n = 38) 였으며, IAT 환자군에서는 94.7%(n = 18), IVI- ACT 환자군에서는 90.9%(n = 20) 의재개통성공률을보였고 양군간의차이는뚜렷하지않았다 (p = 0.64). 재개통에실패한 경우는 3 명 (7.3%) 이었는데내경동맥폐색환자 2 명, 중대뇌동 맥폐색환자 1 명이었다. 시술후뇌출혈은 41 명중 9 명 (22%) 에서나타났고 IAT 환자군과 IVIACT 환자군에서각각 32%(n = 6), 14%(n = 3) 로전자에서더많은비율을보이고있으나통계 적으로유의하지는않았다 (p = 0.17). 증상성뇌출혈은전체환 자가운데 4 명 (10%) 이발생하였으며이중 3 명의환자는뇌실 질내출혈, 1 명은지주막하출혈이었고두환자군간에차이가없 었다 (p = 0.09). 두환자군에서초기신경학적호전은각각 47%, 48% 의비율로나타났고유의한차이는없었다 (p > 0.99). 뇌졸중발병 3 개월후추적관찰이가능한환자는 IAT, IVIACT 환자군에서각각 14 명, 17 명이었고, 이들환자를대상 으로수정 Rankin 척도검사를시행한결과, 좋은예후는각각 36%(n = 5), 59%(n = 10) 로 IVIACT 환자군에서보다더높 은결과를보였지만통계적으로의미있는차이는보이지않았 다 (p = 0.26). Solitaire 를사용한혈관내치료시 10 명의환자들 은필요에따라추가적으로병용요법을사용하였다 ( 풍선혈관성 형술시행 2 명, 스텐트삽입 5 명, Tirofiban 투여 1 명, 풍선혈관 성형술과 Tirofiban 병용사용 1 명, 스텐트와 Tirofiban 병용사 용 1 명 )(Table 3). 추가적치료를받은상기 10 명의환자들은모 Table 1. Clinical Characteristics of the Patients Characteristics Patients (n = 41) Age, yr, median (IQR) 65 (55 76) Male sex, no. (%) 28 (68) Onset to treatment time-hr, median (IQR) 3.4 (1 6) Baseline NIHSS, median (IQR) 12 (10 16) Risk factors, no. (%) Hypertension 22 (53.7) Diabetes 12 (29.3) Heart disease 10 (24.4) Hyperlipidemia 14 (34.2) Previous stroke 5 (12.2) Occluded artery, no. (%) ICA 18 (43.9) MCA 23 (56.1) Recanalization, no. (%) Success 38 (92.7) Fail 3 (7.3) Early improvement, no. (%) 19 (46.3) Intracranial hemorrhage 9 (22.0) Symptomatic intracranial hemorrhage, no. (%) 4 (10.0) Good outcome, no. (%) 15 (48.4)* *Follow-up information was completed 31 patients out of 41 patients. hr = hour, ICA = internal carotid artery, IQR = interquartile range, MCA = middle cerebral artery, NIHSS = National Institute of Health Stroke Score, no. = number, yr = year 348 대한영상의학회지 2016;75(5):346-353 jksronline.org
박소영외 두재개통에성공하였고한명의환자에서증상성뇌출혈소견이있었으며, 3개월후수정 Rankin 척도를확인할수있었던 8 명의환자중 6명에서좋은예후를보였다. 5명의 IAT 환자군과 5명의 IVIACT 환자군간에좋은예후에있어서통계적인차이는없었다 (p > 0.99). 고찰 급성허혈성뇌졸중은사망률및신경학적후유증의비율이매우높은중증질환이다. 특히중대뇌동맥및내경동맥의폐색이있는중증뇌경색환자의경우사망률이 60~85% 에이를정도로예후가불량하고급성기치료법인정맥내혈전용해술을받더라도성공적인혈관의재개통률이낮아보다효과적인치료법에 Table 2. Comparison of Outcome between IAT and IVIACT Characteristics IAT (n = 19) IVIACT (n = 22) p-value Age, yr, median (IQR) 71 (63 81) 59 (50 72) 0.01 Male sex, no. (%) 12 (63.16) 16 (72.73) 0.52 Onset to treatment time-hr, median (IQR) 5.4 (1.5 8.5) 1.6 (0.6 2.0) < 0.01 Baseline-NIHSS, median (IQR) 12 (10 14) 13 (10 16) 0.36 Risk factors, no. (%) Hypertension 13 (68.42) 9 (40.91) 0.08 Diabetes 5 (26.32) 7 (31.82) 0.70 Heart disease 5 (26.32) 5 (22.73) 0.79 Hyperlipidemia 4 (21.05) 10 (45.45) 0.11 Previous stroke 5 (26.32) 0 (0) 0.01 Occluded artery, no. (%) 0.83 ICA 8 (42.11) 10 (45.45) MCA 11 (57.89) 12 (54.55) Recanalization, no. (%) 0.64 Success 18 (94.74) 20 (90.91) Fail 1 (5.26) 2 (9.09) Early improvement, no. (%) 9 (47.37) 10 (47.62) 1.00 Intracranial hemorrhage, no. (%) 6 (31.58) 3 (13.64) 0.17 Symptomatic intracranial hemorrhage, no. (%) 3 (15.79) 1 (4.55) 0.09 Good outcome, no. (%) 5 (35.71)* 10 (58.82)* 0.26 *Follow-up information was completed for 31 patients (14 for IAT, 17 for IVIACT). hr = hour, IAT = intra-arterial therapy, ICA = internal carotid artery, IQR = interquartile range, IVIACT = intravenous and intra-arterial combined therapy, MCA = middle cerebral artery, NIHSS = National Institute of Health Stroke Score, no. = number, yr = year Table 3. The Clinical Characteristics, Detailed Intervention, and Outcome of the Patients Receiving Multimodal Treatment Patient Age Onset to Treatment Time (h) Occluded Artery IV tpa Additional Methods of IA Treatment Recanalization Baseline NIHSS Post NIHSS mrs Symptomatic Hemorrhage 1 63 5.5 ICA No Balloon angioplasy Success 6 0 0 No 2 66 1.5 ICA No Balloon angioplasy Success 9 9 4 No 3 47 10.0 MCA No Balloon angioplasty + tirofiban Success 9 3 2 No 4 54 1.0 ICA No Stent Success 9 1 1 No 5 69 4.5 ICA No Stent + tirofiban Success 10 1 NS* No 6 68 1.3 ICA Yes Stent Success 15 4 2 No 7 74 1.0 ICA Yes Stent Success 10 4 3 No 8 57 1.5 MCA Yes Stent Success 8 3 1 No 9 50 0.5 MCA Yes Stent Success 17 3 1 Yes 10 36 1.0 MCA Yes Tirofiban Success 10 10 NS* No *Not sufficient data. IA = intra-arterial, ICA = internal carotid artery, IV tpa = intra-venous tissue plasminogen activator, MCA = middle cerebral artery, mrs = modified Rankin Scale, NIHSS = National Institute of Health Stroke Score jksronline.org 대한영상의학회지 2016;75(5):346-353 349
대한수요가매우높은질환이다. 그렇기에보다성공적인재개통률을보이는혈관내치료가새로운급성기뇌경색의효과적인치료방법으로각광받고있다 (14, 15). 최근급성기뇌경색환자를대상으로한여러임상연구결과들에서혈관내치료, 특히물리적혈전제거술은매우높은혈관의재개통률을보였으며환자의장기적인예후도향상시킨다는것이입증되었다 (6). 특히 Solitaire 를이용한혈관내치료는폐색된대뇌혈관의재개통성공률이 88~92% 에이르며장기적예후향상에관한근거들이일관되게제시되고있다. Solitaire 는혈관내치료를위하여기존에사용되던 MERCI device 와무작위비교를한 Solitaire with the Intention for Thrombectomy ( 이하 SWIFT) 연구에서재개통률이나장기예후에서우월성을이미입증한바있다 (16). 또한, 증상발생부터 12 시간내의환자들을대상으로시행한다기관무작위배정연구에서스텐트를활용한신속한혈관내치료의사용이대조군에비하여사망률을줄이고기능적인예후를향상시킬수있다고밝힌바있다 (17). 그렇기에실제임상환경에서도뇌혈관중재적시술에많은경험이있는 3차병원들에서는이러한혈관내치료를이미적극적으로시행중이다. 본단일기관연구에서도 Solitaire 를이용한혈관내치료가 90% 이상의높은혈관재개통성공률을보였으며우려되었던부작용인증상성뇌출혈이 10% 미만임을확인할수있었다. 이러한결과는급성기허혈성뇌졸중시혈관내치료의유효성을뒷받침하는근거라고볼수있겠다. 이러한혈관내치료의장점인높은혈관재개통률과함께정맥내혈전용해술의장점이라고할수있는빠른시간에손쉽게치료를시작할수있다는점을결합할수있다면급성기뇌경색환자의예후를보다향상시킬수있을것이다. 그래서정맥내혈전용해술을시행한뒤에이어서혈관내치료를사용하는방식인 IVIACT 의시도가활발히시행되고있는추세이다. 이번연구에서 IAT 환자군과 IVIACT 환자군에서혈관재개통률과출혈빈도, 초기신경학적호전정도가유사한수준을나타내고있었다. 장기적인신경학적예후는두환자군간에비록통계적인차이는없었지만 IVIACT 환자군에서좋은예후의비율이더높게나타났다. 이러한자료들은 IVIACT 방법이안전성측면에서 IAT 와비교했을때적어도유사한정도의수준을유지한다는것을시사하는결과이다. IAT 와비교하여 IVIACT 의안전성과효과를보고자했던이전의연구들에서도본연구와동일한결과들을확인할수있다 (18, 19). 하지만이전의결과들이대규모연구를통한임상적인근거를충분히획득하지못한반면, 최근다수의대규모무작위배정연구가성공적으로결론지어지면서 IVI- ACT 의안정성과효능성이보다확고하게인정받고있다 (6, 20). 전순환의근위부가폐색된급성뇌경색환자에서 IV tpa 단독으로사용하는환자와 Solitaire 를이용한 IVIACT 로치료한환자를비교해본임상연구에서도안전성에있어서는 IV tpa 단독으로사용한환자군과유사한정도를보였으나장기적인예후및기능적인회복정도에있어서는통계학적의의는없었지만 IVIACT 가우월성을보였다 (21). 혈관내치료시막힌혈전이혈관내벽에단단히붙어있어자가팽창형스텐트로개통되기어렵거나재협착이염려되는경우, 또는혈전제거이후심각한혈관연축이발생하는등의경우에서혈전제거술에연이어스텐트삽입이나풍선혈관성형술등을시행하는경우들이있다. 아직대규모연구는부족하지만이러한병용요법을시행했을때증상성출혈과같이우려되었던위험성이 Solitaire 단독시행에비해의미있게증가하지않고재개통률또한만족스러운결과를내고있다 (22, 23). 이번연구에서도병용요법의사례들을개별적으로살펴보았고각각의방법이얼마나효과적이었는지통계적인분석을시행하지는못했지만비교적안전하였고재개통률또한매우높음을확인하였다. 다만, 우리연구를포함한그동안의연구에있어서, 표본크기가작고혈관선택에제한이있다는등의한계를가지고있고, 높은재개통률이장기적인기능회복과도충분한연관성이보이는지에대해서는추가적인확인이필요한상태이다. 본연구는단일기관의임상적경험을바탕으로한것으로, 참여한환자의수가적고두비교군사이의연령대가차이를보이고있어서해석에주의를요한다는한계를가지고있다. 두환자군사이에연령이뚜렷이차이나는것은우리나라에서정맥내혈전용해술을시행시 80 세이상에서는 tpa 의사용이제한되고있어이러한고령의환자가 IVIACT 에포함되지못했기때문인것으로생각된다. 또다른한계점으로는, 두환자군사이에치료시작까지의시간이크게차이가난다는점을들수있다. 치료시작시간의차이는, IAT 가증상발현으로부터비교적지연되더라도시도가가능한데비해 IV tpa 는 4.5시간이라는제약이있는데서기인하는예측가능한결과였다 (24). 하지만치료시작까지걸리는시간에따라재관류치료후예후및부작용에상당한영향을받는다는점을고려해볼때, IVIACT 나병용요법시에도비교적안전한결과가나온것에대한해석에는주의를요한다고할수있다. 본연구가특정조건을미리정해놓고가이드라인에맞는환자군을모집하여결과를분석한것이아니라, 환자개개인의임상적, 영상학적특성에맞추어치료시작까지의시간기준과치료의방법을달리적용했을때환자의전반적인예후및부작용의발생빈도가어떠한지에대한우리기관의임상경험을분석한내용이기때문에이를일반화시키기에는많은한계가있다. 따라서본연구는추후혈관내치료의대상환자를선별할때시간적인요소이외에도관류확산불일치 (perfu- 350 대한영상의학회지 2016;75(5):346-353 jksronline.org
박소영외 sion-diffusion mismatch) 나곁순환등의영상학적소견을참고해서결정하는것이도움이되었다는임상적경험을보고하면서, 추후좀더확실한가이드가인을만들기위한전향적인대규모연구가뒷받침되어야함을확인하는연구라고할수있겠다. 이번연구는단일기관의전순환부위의급성허혈성뇌졸중환자에서의 Solitaire 를이용한혈관내치료에관한후향적관찰연구이다. Solitaire 를이용한혈관내치료는재개통률이우수하였고, 정맥내혈전용해술이나기타다양한병용요법을함께사용하여도그위험성이뚜렷하게증가되지않았다. 따라서급성허혈성뇌졸중치료시잘선별된환자의경우 Solitaire 를비롯하여보다다각도의적극적인치료가환자증상호전에도움이될것으로여겨진다. REFERENCES 1. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017-1025 2. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998;352:1245-1251 3. Riedel CH, Zimmermann P, Jensen-Kondering U, Stingele R, Deuschl G, Jansen O. The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke 2011;42: 1775-1777 4. Lee M, Hong KS, Saver JL. Efficacy of intra-arterial fibrinolysis for acute ischemic stroke: meta-analysis of randomized controlled trials. Stroke 2010;41:932-937 5. Roth C, Papanagiotou P, Behnke S, Walter S, Haass A, Becker C, et al. Stent-assisted mechanical recanalization for treatment of acute intracerebral artery occlusions. Stroke 2010;41:2559-2567 6. Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et al. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015;46: 3020-3035 7. de Los Ríos la Rosa F, Khoury J, Kissela BM, Flaherty ML, Alwell K, Moomaw CJ, et al. Eligibility for intravenous recombinant tissue-type plasminogen activator within a population: the Effect of the European Cooperative Acute Stroke Study (ECASS) III Trial. Stroke 2012;43:1591-1595 8. Cho KH, Ko SB, Kim DH, Park HK, Cho AH, Hong KS, et al. Focused update of Korean clinical practice guidelines for the thrombolysis in acute stroke management. Korean J Stroke 2012;14:95-105 9. Deshmukh VR, Fiorella DJ, Albuquerque FC, Frey J, Flaster M, Wallace RC, et al. Intra-arterial thrombolysis for acute ischemic stroke: preliminary experience with platelet glycoprotein IIb/IIIa inhibitors as adjunctive therapy. Neurosurgery 2005;56:46-54; discussion 54-55 10. 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 11. Wilson JT, Hareendran A, Grant M, Baird T, Schulz UG, Muir KW, et al. Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin Scale. Stroke 2002;33:2243-2246 12. Fugate JE, Klunder AM, Kallmes DF. What is meant by TICI? AJNR Am J Neuroradiol 2013;34:1792-1797 13. Mazya M, Egido JA, Ford GA, Lees KR, Mikulik R, Toni D, et al. Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: safe Implementation of Treatments in Stroke (SITS) symptomatic intracerebral hemorrhage risk score. Stroke 2012;43:1524-1531 14. Schwab S, Steiner T, Aschoff A, Schwarz S, Steiner HH, Jansen O, et al. Early hemicraniectomy in patients with complete middle cerebral artery infarction. Stroke 1998;29: 1888-1893 15. Flint AC, Duckwiler GR, Budzik RF, Liebeskind DS, Smith WS; MERCI and Multi MERCI Writing Committee. Mechanical thrombectomy of intracranial internal carotid jksronline.org 대한영상의학회지 2016;75(5):346-353 351
occlusion: pooled results of the MERCI and Multi MERCI Part I trials. Stroke 2007;38:1274-1280 16. Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012;380:1241-1249 17. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372:1019-1030 18. Zaidat OO, Suarez JI, Santillan C, Sunshine JL, Tarr RW, Paras VH, et al. Response to intra-arterial and combined intravenous and intra-arterial thrombolytic therapy in patients with distal internal carotid artery occlusion. Stroke 2002;33:1821-1826 19. Wolfe T, Suarez JI, Tarr RW, Welter E, Landis D, Sunshine JL, et al. Comparison of combined venous and arterial thrombolysis with primary arterial therapy using recombinant tissue plasminogen activator in acute ischemic stroke. J Stroke Cerebrovasc Dis 2008;17:121-128 20. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015; 372:11-20 21. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. Stent-retriever thrombectomy after intravenous t-pa vs. t-pa alone in stroke. N Engl J Med 2015;372:2285-2295 22. Park JH, Park SK, Jang KS, Jang DK, Han YM. Critical use of balloon angioplasty after recanalization failure with retrievable stent in acute cerebral artery occlusion. J Korean Neurosurg Soc 2013;53:77-82 23. Mordasini P, Brekenfeld C, Byrne JV, Fischer U, Arnold M, Heldner MR, et al. Technical feasibility and application of mechanical thrombectomy with the Solitaire FR Revascularization Device in acute basilar artery occlusion. AJNR Am J Neuroradiol 2013;34:159-163 24. Del Zoppo GJ, Saver JL, Jauch EC, Adams HP Jr; American Heart Association Stroke Council. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke 2009;40:2945-2948 352 대한영상의학회지 2016;75(5):346-353 jksronline.org
박소영외 박소영 1 이한빈 2 김종욱 2 오승헌 2 김진권 2 김남근 3 김상흠 4 김옥준 2 * 목적 : 급성허혈성뇌졸중환자를대상으로혈관내치료를시행한환자군 (Intra-arterial therapy; 이하 IAT) 과, 먼저정맥내혈전용해술을시행한후이어서혈관내치료를시행한환자군 (Intra-venous and intra-arterial combined therapy; 이하 IVIACT) 사이에안전성과효용성을비교분석하였다. 대상과방법 : 전순환의폐색이있는급성허혈성뇌졸중환자중 Solitaire 를이용한기계적혈전제거술을시행한 41 명을대상으로후향적으로연구하였다. IAT 를시행한환자군은 19 명, IVIACT 를시행한환자군은 22 명이었으며전체환자중 10 명은병용요법을시행하였다. 시술후혈관재개통성공유무및예후와부작용에대해분석하였다. 결과 : 전반적인재개통비율은 93% 에이르렀고증상성출혈은 10% 에서발생하였다. IAT 와 IVIACT 환자군간에뇌출혈빈도, 재개통비율, 초기신경학적호전정도에있어서유의미한차이는없었다. 좋은예후에있어서는두환자군간에통계적인차이는없었지만 IAT 환자군에서 36% 를보인데비해 IVIACT 환자군에서 59% 로더높은비율을나타내었다 (p = 0.26). 병용요법을시행한환자에서출혈의부작용은뚜렷이증가하지않았다. 결론 : 급성허혈성뇌졸중환자에서의 Solitaire 를이용한혈관내치료는재개통률이우수하였고, 정맥내혈전용해술이나기타다양한병용요법을함께사용하여도그위험성이뚜렷하게증가되지않음을확인하였다. 1 서울특별시보라매병원신경과, 차의과학대학교분당차병원 2 신경과, 4 영상의학과, 3 차의과학대학교임상의학연구소 jksronline.org 대한영상의학회지 2016;75(5):346-353 353