癌症相关缺血性卒中临床研究
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摘要
目的探讨肿瘤患者发生缺血性卒中的影响因素、生化指标、病因,以及影像学特点,以提高临床认识。方法收集2018年4月至2019年1月收治的693例缺血性卒中患者临床资料,比较缺血性卒中伴活动性癌症组(癌症组,31例)与传统急性缺血性卒中不伴癌症组(对照组,662例)入院时社会人口学数据、脑卒中危险因素、入院时美国国立卫生研究院卒中量表(NIHSS)评分,血小板计数、D-二聚体、纤维蛋白原、C-反应蛋白水平,扩散加权成像(DWI)显示的梗死灶特点[急性多发性缺血病变(AMIMCT)],记录癌症组患者肿瘤类型及组织学分型差异。采用单因素和多因素后退法Logistic回归分析癌症相关缺血性卒中的影响因素。结果与对照组相比,癌症组患者年龄偏高(χ~2=2.148,P=0.032),高血压(χ~2=5.425,P=0.020)和高脂血症(Fisher确切概率法:P=0.000)比例低;血清D-二聚体(Z=2687.500,P=0.001)、纤维蛋白原(t=2.402,P=0.022)和C-反应蛋白(Z=3669.000,P=0.001)水平升高。两组TOAST分型差异具有统计学意义(Fisher确切概率法:P=0.000),与对照组相比,癌症组大动脉粥样硬化(LAA)型比例较低(Fisher确切概率法:P=0.000),不明病因(SUE)型比例较高(χ~2=175.418,P=0.000);而AMIMCT比例较高(χ~2=22.560,P=0.000)。多因素后退法Logistic回归分析显示,癌症组患者缺乏高脂血症病史(OR=0.188,95%CI:0.048～0.730;P=0.016),而SUE型(OR=29.854,95%CI:10.310～86.449;P=0.000)以及高水平的血清D-二聚体(OR=1.663,95%CI:1.294～2.137;P=0.000)和纤维蛋白原(OR=1.785,95%CI:1.294～2.137;P=0.000)是其危险因素。结论癌症相关缺血性卒中患者常缺乏大动脉粥样硬化证据,血清D-二聚体和纤维蛋白原水平升高,以及SUE型提示此类患者可能存在高凝状态和栓塞机制。
Objective To explore the influencing factors, hiomarkers, etiology and imaging features of cancer-associated ischemic stroke. Methods The clinical data of 693 patients with ischemic stroke from April 2018 to January 2019 were retrospectively collected. The patients were divided into ischemic stroke with active cancer(cancer group, N = 31) and traditional ischemic stroke(control group, N = 662).The sociodemographic data, risk factors for stroke, National Institutes of Health Stroke Scale(NIHSS) scores on admission, platelet count, D-dimer, fibrinogen and C-reactive protein(CRP) level, features of infarcts on diffusion-weighted imaging [DWI, which was acute multiple ischemic lesions located in more than one vascular territories(AMIMCT)], and the tumor type and histological classification in cancer group were recorded. Univariate and multivariate backward Logistic regression analysis were used to analyze the influencing factors of cancer-associated ischemic stroke. Results Compared with control group, patients in cancer group had older age(X~2= 2.148, P = 0.032), lower proportion of hypertension(X~2=5.425, P = 0.020)and hyperlipidemia(Fisher exact probability: P = 0.000), and elevated levels of serum D-dimer(Z =2687.500, P= 0.001), fibrinogen(t = 2.402, P = 0.022) and CRP(Z = 3669.000, P = 0.001). There was significant difference between 2 groups on TOAST(Fisher exact probability: P = 0.000). Patients in cancer group had lower proportion of large artery atherosclerosis(LAA; Fisher exact probability: P= 0.000), but higher proportion of stroke of undetermined etiology(SUE; X~2= 175.418, P = 0.000) and AMIMCT(X~2=22.560, P = 0.000). Multivariate backward Logistic regression analysis showed having no history of hyperlipidemia(OR= 0.188, 95%CI: 0.048-0.730; P = 0.016), SUE(OR=29.854, 95%CI: 10.310-86.449;P = 0.000), elevated levels of D-dimer(OR= 1.663, 95% CI: 1.294-2.137; P = 0.000) and fibrinogen(OR =1.785, 95% CI: 1.294-2.137; P = 0.000) were risk factors for cancer-associated ischemic stroke.Conclusions It is usually lack of evidence of LA A for cancer-associated ischemic stroke. Elevated Ddimer and fibrinogen, and SUE demonstrated that hypercoagulability and microembolus embolism may be the possible mechanism of cancer-associated ischemic stroke.
Objective To explore the influencing factors, hiomarkers, etiology and imaging features of cancer-associated ischemic stroke. Methods The clinical data of 693 patients with ischemic stroke from April 2018 to January 2019 were retrospectively collected. The patients were divided into ischemic stroke with active cancer(cancer group, N = 31) and traditional ischemic stroke(control group, N = 662).The sociodemographic data, risk factors for stroke, National Institutes of Health Stroke Scale(NIHSS) scores on admission, platelet count, D-dimer, fibrinogen and C-reactive protein(CRP) level, features of infarcts on diffusion-weighted imaging [DWI, which was acute multiple ischemic lesions located in more than one vascular territories(AMIMCT)], and the tumor type and histological classification in cancer group were recorded. Univariate and multivariate backward Logistic regression analysis were used to analyze the influencing factors of cancer-associated ischemic stroke. Results Compared with control group, patients in cancer group had older age(X~2= 2.148, P = 0.032), lower proportion of hypertension(X~2=5.425, P = 0.020)and hyperlipidemia(Fisher exact probability: P = 0.000), and elevated levels of serum D-dimer(Z =2687.500, P= 0.001), fibrinogen(t = 2.402, P = 0.022) and CRP(Z = 3669.000, P = 0.001). There was significant difference between 2 groups on TOAST(Fisher exact probability: P = 0.000). Patients in cancer group had lower proportion of large artery atherosclerosis(LAA; Fisher exact probability: P= 0.000), but higher proportion of stroke of undetermined etiology(SUE; X~2= 175.418, P = 0.000) and AMIMCT(X~2=22.560, P = 0.000). Multivariate backward Logistic regression analysis showed having no history of hyperlipidemia(OR= 0.188, 95%CI: 0.048-0.730; P = 0.016), SUE(OR=29.854, 95%CI: 10.310-86.449;P = 0.000), elevated levels of D-dimer(OR= 1.663, 95% CI: 1.294-2.137; P = 0.000) and fibrinogen(OR =1.785, 95% CI: 1.294-2.137; P = 0.000) were risk factors for cancer-associated ischemic stroke.Conclusions It is usually lack of evidence of LA A for cancer-associated ischemic stroke. Elevated Ddimer and fibrinogen, and SUE demonstrated that hypercoagulability and microembolus embolism may be the possible mechanism of cancer-associated ischemic stroke.
引文
[1]GBD 2013 Mortality and Causes of Death Collaborators.Global,regional,and national age-sex specific all-cause and causespecific mortality for 240 causes of death,1990-2013:a systematic analysis for the Global Burden of Disease Study 2013[J].Lancet,2015,385:117-171.
[2]China Disease Control and Prevention Center of Chronic Noncommunicable Diseases.China Death Cause Surveillance Data Set 2015[M].Beijing:China Science and Technology Press,2016:27[.中国疾病预防控制中心慢性非传染性疾病预防控制中心.中国死因监测数据集2015[M].北京:中国科学技术出版社,2016:27.]
[3]Grazioli S,Paciaroni M,Agnelli G,Acciarresi M,Alberti A,D'Amore C,Caso V,Venti M,Guasti L,Ageno W,Squizzato A. Cancer-associated ischemic stroke:a retrospective multicenter cohort study[J].Thromb Res,2018,165:33-37.
[4]Corse AK,Kurtis H.Ischemic stroke caused by secondary polycythemia and incidentally-found renal cell carcinoma:a case repor[tJ].Am J Case Rep,2018,19:638-641.
[5]Bonnerot M,Humbertjean L,Mione G,Lacour JC,Derelle AL,Sanchez JC,Riou-Comte N,Richard S.Cerebral ischemic events in patients with pancreatic cancer:a retrospective cohort study of 17 patients and a literature review[J].Medicine(Baltimore),2016,95:E4009.
[6]Cerebrovascular Disease Study Group,Chinese Society of Neurology,Chinese Medical Association.Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018[J].Zhonghua Shen Jing Ke Za Zhi,2018,51:666-682[.中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2018[J].中华神经科杂志,2018,51:666-682.]
[7]Kassubek R,Bullinger L,Kassubek J,Dreyhaupt J,Ludolph AC,Althaus K,Lewerenz J.Identifying ischemic stroke associated with cancer:a multiple model derived from a casecontrol analysis[J].J Neurol,2017,264:781-791.
[8]Naito H,Nezu T,Hosomi N,Aoki S,Ueno H,Ochi K,Maruyama H.Antithrombotic therapy strategy for cancerassociated ischemic stroke:a case series of 26 patients[J].JStroke Cerebrovasc Dis,2018,27:E206-211.
[9]Trousseau A.Phlegmasia alba dolens[J].Clin Med Hotel-dieu Paris,1865,3:654-712.
[10]Ishikawa M,Nakayama K,Ishibashi T,Sato E,Nakamura K,Katagiri H,Kyo S.Case series of cerebral infarction with Trousseau's syndrome associated with malignant gynecological tumors[J].Mol Clin Oncol,2016,5:138-142.
[11]Ladizinski B,Federman DG.Trousseau syndrome[J].CMAJ,2013,185:1063.
[12]Matsunaga M,Fukahori M,Ushijima T,Miwa K.Trousseau's syndrome in a patient with gastric cancer[J].BMJ Case Rep,2015:ID2015213284.
[13]Quintas S,Rogado J,Gullón P,Pacheco-Barcia V,Dotor GarcíaSoto J,Reig-RosellóG,Mondéjar R,Colomer R,Vivancos J.Predictors of unknown cancer in patients with ischemic stroke[J].J Neurooncol,2018,137:551-557.
[14]Selvik HA,Thomassen L,Bjerkreim AT,N?ss H.Cancerassociated stroke:the Bergen NORSTROKE study[J].Cerebrovasc Dis Extra,2015,5:107-113.
[15]Gon Y,Okazaki S,Terasaki Y,Sasaki T,Yoshimine T,Sakaguchi M,Mochizuki H.Characteristics of cryptogenic stroke in cancer patients[J].Ann Clin Transl Neurol,2016,3:280-287.
[16]Lee EJ,Nah HW,Kwon JY,Kang DW,Kwon SU,Kim JS.Ischemic stroke in patients with cancer:is it different from usual strokes[J]?Int J Stroke,2014,9:406-412.
[17]Chung JW,Park SH,Kim N,Kim WJ,Park JH,Ko Y,Yang MH,Jang MS,Han MK,Jung C,Kim JH,Oh CW,Bae HJ.Trial of ORG 10 172 in Acute Stroke Treatment(TOAST)classification and vascular territory of ischemic stroke lesions diagnosed by diffusion-weighted imaging[J].J Am Heart Assoc,2014,3:E001119.
[18]Schwarzbach CJ,Schaefer A,Ebert A,Held V,Bolognese M,Kablau M,Hennerici MG,Fatar M.Stroke and cancer:the importance of cancer-associated hypercoagulation as a possible stroke etiology[J].Stroke,2012,43:3029-3034.
[19]Kim SJ,Park JH,Lee M,Park YG,Ahn M,Bang OY.Clues to occult cancer in patients with ischemic stroke[J].PLoS One,2012,7:E44959.
[20]Finelli PF,Nouh A.Three-territory DWI acute infarcts:diagnostic value in cancer-associated hypercoagulation stroke(Trousseau syndrome)[J].AJNR Am J Neuroradiol,2016,37:2033-2036.
[21]Gon Y,Sakaguchi M,Takasugi J,Kawano T,Kanki H,Watanabe A,Oyama N,Terasaki Y,Sasaki T,Mochizuki H.Plasma D-dimer levels and ischaemic lesions in multiple vascular regions can predict occultcancer in patients with cryptogenic stroke[J].Eur J Neurol,2017,24:503-508.
[22]Neilson LE,Rogers LR,Sundararajan S.Evaluation and treatment of a patient with recurrent stroke in the setting of active malignancy[J].Stroke,2018[.Epub ahead of print]
[23]Liu J,Frishman WH.Nonbacterial thrombotic endocarditis:pathogenesis,diagnosis,and management[J].Cardiol Rev,2016,24:244-247.
[24]Kim K,Lee J.Risk factors and biomarkers of ischemic stroke in cancer patients[J].J Stroke,2014,16:91-96.
[25]Selvik HA,Bjerkreim AT,Thomassen L,Waje-Andreassen U,Naess H,Kvistad CE.When to screen ischaemic stroke patients for cance[rJ].Cerebrovasc Dis,2018,45(1/2):42-47.
[26]Wahrenbrock M,Borsig L,Le D,Varki N,Varki A.Selectinmucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas[J].J Clin Invest,2003,112:853-862.
[27]Diakos CI,Charles KA,McMillan DC,Clarke SJ.Cancerrelated inflammation and treatment effectiveness[J].Lancet Oncol,2014,15:E493-503.
[28]Seok JM,Kim SG,Kim JW,Chung CS,Kim GM,Lee KH,Bang OY.Coagulopathy and embolic signal in cancer patients with ischemic stroke[J].Ann Neurol,2010,68:213-219.2019-05-15
[2]China Disease Control and Prevention Center of Chronic Noncommunicable Diseases.China Death Cause Surveillance Data Set 2015[M].Beijing:China Science and Technology Press,2016:27[.中国疾病预防控制中心慢性非传染性疾病预防控制中心.中国死因监测数据集2015[M].北京:中国科学技术出版社,2016:27.]
[3]Grazioli S,Paciaroni M,Agnelli G,Acciarresi M,Alberti A,D'Amore C,Caso V,Venti M,Guasti L,Ageno W,Squizzato A. Cancer-associated ischemic stroke:a retrospective multicenter cohort study[J].Thromb Res,2018,165:33-37.
[4]Corse AK,Kurtis H.Ischemic stroke caused by secondary polycythemia and incidentally-found renal cell carcinoma:a case repor[tJ].Am J Case Rep,2018,19:638-641.
[5]Bonnerot M,Humbertjean L,Mione G,Lacour JC,Derelle AL,Sanchez JC,Riou-Comte N,Richard S.Cerebral ischemic events in patients with pancreatic cancer:a retrospective cohort study of 17 patients and a literature review[J].Medicine(Baltimore),2016,95:E4009.
[6]Cerebrovascular Disease Study Group,Chinese Society of Neurology,Chinese Medical Association.Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018[J].Zhonghua Shen Jing Ke Za Zhi,2018,51:666-682[.中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2018[J].中华神经科杂志,2018,51:666-682.]
[7]Kassubek R,Bullinger L,Kassubek J,Dreyhaupt J,Ludolph AC,Althaus K,Lewerenz J.Identifying ischemic stroke associated with cancer:a multiple model derived from a casecontrol analysis[J].J Neurol,2017,264:781-791.
[8]Naito H,Nezu T,Hosomi N,Aoki S,Ueno H,Ochi K,Maruyama H.Antithrombotic therapy strategy for cancerassociated ischemic stroke:a case series of 26 patients[J].JStroke Cerebrovasc Dis,2018,27:E206-211.
[9]Trousseau A.Phlegmasia alba dolens[J].Clin Med Hotel-dieu Paris,1865,3:654-712.
[10]Ishikawa M,Nakayama K,Ishibashi T,Sato E,Nakamura K,Katagiri H,Kyo S.Case series of cerebral infarction with Trousseau's syndrome associated with malignant gynecological tumors[J].Mol Clin Oncol,2016,5:138-142.
[11]Ladizinski B,Federman DG.Trousseau syndrome[J].CMAJ,2013,185:1063.
[12]Matsunaga M,Fukahori M,Ushijima T,Miwa K.Trousseau's syndrome in a patient with gastric cancer[J].BMJ Case Rep,2015:ID2015213284.
[13]Quintas S,Rogado J,Gullón P,Pacheco-Barcia V,Dotor GarcíaSoto J,Reig-RosellóG,Mondéjar R,Colomer R,Vivancos J.Predictors of unknown cancer in patients with ischemic stroke[J].J Neurooncol,2018,137:551-557.
[14]Selvik HA,Thomassen L,Bjerkreim AT,N?ss H.Cancerassociated stroke:the Bergen NORSTROKE study[J].Cerebrovasc Dis Extra,2015,5:107-113.
[15]Gon Y,Okazaki S,Terasaki Y,Sasaki T,Yoshimine T,Sakaguchi M,Mochizuki H.Characteristics of cryptogenic stroke in cancer patients[J].Ann Clin Transl Neurol,2016,3:280-287.
[16]Lee EJ,Nah HW,Kwon JY,Kang DW,Kwon SU,Kim JS.Ischemic stroke in patients with cancer:is it different from usual strokes[J]?Int J Stroke,2014,9:406-412.
[17]Chung JW,Park SH,Kim N,Kim WJ,Park JH,Ko Y,Yang MH,Jang MS,Han MK,Jung C,Kim JH,Oh CW,Bae HJ.Trial of ORG 10 172 in Acute Stroke Treatment(TOAST)classification and vascular territory of ischemic stroke lesions diagnosed by diffusion-weighted imaging[J].J Am Heart Assoc,2014,3:E001119.
[18]Schwarzbach CJ,Schaefer A,Ebert A,Held V,Bolognese M,Kablau M,Hennerici MG,Fatar M.Stroke and cancer:the importance of cancer-associated hypercoagulation as a possible stroke etiology[J].Stroke,2012,43:3029-3034.
[19]Kim SJ,Park JH,Lee M,Park YG,Ahn M,Bang OY.Clues to occult cancer in patients with ischemic stroke[J].PLoS One,2012,7:E44959.
[20]Finelli PF,Nouh A.Three-territory DWI acute infarcts:diagnostic value in cancer-associated hypercoagulation stroke(Trousseau syndrome)[J].AJNR Am J Neuroradiol,2016,37:2033-2036.
[21]Gon Y,Sakaguchi M,Takasugi J,Kawano T,Kanki H,Watanabe A,Oyama N,Terasaki Y,Sasaki T,Mochizuki H.Plasma D-dimer levels and ischaemic lesions in multiple vascular regions can predict occultcancer in patients with cryptogenic stroke[J].Eur J Neurol,2017,24:503-508.
[22]Neilson LE,Rogers LR,Sundararajan S.Evaluation and treatment of a patient with recurrent stroke in the setting of active malignancy[J].Stroke,2018[.Epub ahead of print]
[23]Liu J,Frishman WH.Nonbacterial thrombotic endocarditis:pathogenesis,diagnosis,and management[J].Cardiol Rev,2016,24:244-247.
[24]Kim K,Lee J.Risk factors and biomarkers of ischemic stroke in cancer patients[J].J Stroke,2014,16:91-96.
[25]Selvik HA,Bjerkreim AT,Thomassen L,Waje-Andreassen U,Naess H,Kvistad CE.When to screen ischaemic stroke patients for cance[rJ].Cerebrovasc Dis,2018,45(1/2):42-47.
[26]Wahrenbrock M,Borsig L,Le D,Varki N,Varki A.Selectinmucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas[J].J Clin Invest,2003,112:853-862.
[27]Diakos CI,Charles KA,McMillan DC,Clarke SJ.Cancerrelated inflammation and treatment effectiveness[J].Lancet Oncol,2014,15:E493-503.
[28]Seok JM,Kim SG,Kim JW,Chung CS,Kim GM,Lee KH,Bang OY.Coagulopathy and embolic signal in cancer patients with ischemic stroke[J].Ann Neurol,2010,68:213-219.2019-05-15