以急性多发性脑梗死为首发表现的Trousseau综合征临床特征分析

doi:10.3969/j.issn.1006-9771.2020.06.020

摘要/Abstract

摘要：

目的研究以急性多发性脑梗死(AMCI)为首发表现的Trousseau综合征的临床特征。方法回顾性分析2012年1月至2019年1月本院神经内科收治的19例以AMCI为首发表现的Trousseau综合征患者,对其临床表现、影像学特征、实验室检查、治疗方法及预后进行分析。结果 19例患者平均年龄(71.05±10.59)岁,其中男性10例,女性9例。梗死影像表现为多发点状或片状病灶,15例(78.95%)显示双侧梗死,11例(57.89%)为多血管流域多发小病灶(< 20 mm),9例(52.94%)并发脑动脉狭窄,其中7例(77.78%)梗死病灶分布与狭窄血管供血区不一致。所有患者D-二聚体升高,中位数3.08 mg/L (0.79~7.00 mg/L),8例心肌肌钙蛋白I (cTnI)升高,17例糖类抗原125 (CA125)升高。15例(78.94%)接受抗血小板治疗的患者中,5例(33.3%)联合抗凝治疗。9例(47.37%)住院期间出现早期神经功能恶化(7例)或脑梗死复发(2例)。随访30 d内死亡5例,90 d累计发生复发血栓栓塞事件6次,脑梗死和下肢静脉血栓各3次,90 d内死亡13例(68.42%)。结论 AMCI可作为Trousseau综合征的首发表现,对于双侧梗死小病灶或与脑血管狭窄供血区分布不一致的多发病灶,结合升高的D-二聚体、cTnI和CA125,应考虑到恶性肿瘤引起高凝状态导致Trousseau综合征的可能,筛查隐匿性肿瘤,积极治疗肿瘤改善预后。

关键词: Trousseau综合征, 脑梗死, 恶性肿瘤, 高凝状态, 肌钙蛋白

Abstract:

Objective To investigate the clinical features of Trousseau's syndrome with acute multiple cerebral infarction (AMCI) as the first manifestation.Methods From January, 2012 to January, 2019, a retrospective study was conducted on 19 patients with AMCI diagnosed as the first manifestation of Trousseau's syndrome. The clinical data, imaging features, laboratory results, treatment, and prognosis data were collected and analyzed.Results They were (71.05±10.59) years old, with ten males and nine females. MRI-diffusion weighted imaging (DWI) showed numerous small lesions with or without large area cerebral infarction in multiple vascular territories. Fifteen cases (78.95%) showed bilateral infarction, eleven cases (57.89%) showed multiple small lesions (< 20 mm) in multiple vascular territories, nine cases showed cerebral artery stenosis, in which seven cases (77.78%) of cerebral infarction lesions were not consistent with stenotic vessels. All patients had elevated levels of D-dimer with a median of 3.08 mg/L (0.79~7.00 mg/L). Cardiac troponin I (cTnI) increased in eight cases. CA125 increased in 17 cases. Among the 15 cases treated with antiplatelet therapy, five cases (33.3%) were combined with anticoagulation therapy. Nine cases (47.37%) developed early neurological function deterioration or recurrent cerebral infarction during hospitalization. After the follow-up, five cases died within 30 days, and six recurrent thrombotic events occurred within 90 days, including three events for cerebral infarction and three events for lower limb venous thrombosis, and finally 13 cases (68.42%) died within 90 days.Conclusion AMCI can be the first manifestation of Trousseau's syndrome. The image features including bilateral small infarction or multiple lesions being not consistent with the stenotic vessels, combined with the elevated levels of D-dimer, cTnI and CA125, can be the clues to Trousseau's syndrome caused by hypercoagulability due to cancer. Timely screening for occult cancer and active anticancer therapy may be helpful to improve their outcome.

Key words: Trousseau's syndrome, cerebral infarction, cancer, hypercoagulability, troponin

中图分类号:

R743.3

郭琳佳,陈靖,高凤莲,张运,刘文宏. 以急性多发性脑梗死为首发表现的Trousseau综合征临床特征分析[J]. 《中国康复理论与实践》, 2020, 26(6): 730-737.

GUO Lin-jia,CHEN Jing,GAO Feng-lian,ZHANG Yun,LIU Wen-hong. Clinical Features of Trousseau's Syndrome with Acute Multiple Cerebral Infarction as the First Manifestation[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(6): 730-737.

图/表 2

表1

以AMCI为首发表现的Trousseau综合征患者的临床资料"

编号	年龄(岁)/性别	肿瘤类型	肿瘤分期	肿瘤确诊距AMCI间隔(月)	传统脑卒中危险因素	NIHSS (入院时)	MRI-DWI	病灶分布	脑血管狭窄	D-D (mg/L)(入院时)	cTnI (ng/ml)(入院时)	异常肿瘤标记物	抗栓治疗	复发血栓栓塞事件	90 d mRS
1	59/男	胰腺癌	Ⅳ	0	+	2	MSLM	双侧前+后循环	B: PCA	35.64	0.25	CA125,CA199,CA153,CEA,NSE	抗血小板	-	6
2	65/女	结肠癌	Ⅳ	0	+	16	MSLM	双侧前+后循环	L: MCA	12.98	0.29	CA125,CA199,CEA	抗血小板+抗凝	-	6
3	65/女	腹膜癌	Ⅳ	0	+	2	MSM	双侧前+后循环	-	0.79	0.01	CA125,NSE	抗血小板	-	3
4	66/男	肺腺癌	不详	0	+	22	MSLM	双侧前循环	R: ICA	6.70	0.06	CA125,CA153,NSE	抗血小板	-	6
5	83/男	前列腺癌	Ⅳ	0	+	4	MSM	单侧前+后循环	-	0.49	0.02	CEA,TPSA	抗血小板	失访	失访
6	66/女	胰腺癌	Ⅳ	0	+	5	MSLM	双侧前+后循环	R: MCA	9.41	0.16	CA125,CA199,CEA	抗血小板+抗凝	失访	失访
7	58/女	卵巢癌	Ⅳ	0	+	0	MSM	双侧前循环	未查	0.93	0.01	CA125	抗凝	-	0
8	80/男	胰腺癌	Ⅳ	0	+	2	MSM	双侧前循环	B: ICA L: MCA	3.08	0.04	CA125,CA199,CEA	抗血小板	CI	6
9	90/男	肝癌	Ⅳ	24	+	1	MSM	单侧前+后循环	R: MCA	3.32	0.02	CA125,CA153,NSE,AFP	抗血小板	DVT	6
10	86/男	肺癌	不详	24	-	7	MSLS	单侧前循环	B: ICA	7.00	0.01	CA125,CA199,CA153,CEA	抗凝	DVT	6
11	87/男	肺癌	不详	18	+	6	MSM	双侧前循环	L: MCA	0.36	0.16	CA125,NSE,CEA	抗血小板	-	6
12	78/女	肺癌	不详	2	+	19	MSLM	双侧前+后循环	未查	4.57	0.42	CA125,NSE,CEA	抗血小板+抗凝	-	6
13	62/女	乳腺癌	不详	24	+	3	MSM	双侧前循环	-	0.29	0.01	-	抗血小板	-	0
14	73/女	甲状腺癌	Ⅳ	2	-	2	MSLM	双侧前+后循环	-	2.02	0.01	CA125,CA153,CEA	-	CI+DVT	6
15	77/男	胃癌	Ⅳ	4	+	6	MSM	双侧前+后循环	-	3.07	未查	CA125,CA199,CA153,CEA	-	-	6
16	57/男	肺腺癌	II	2	-	2	MSLS	单侧前循环	-	2.51	未查	CA125,CA153,NSE	抗血小板	-	6
17	59/女	卵巢癌	Ⅳ	1	_	6	MSM	双侧前+后循环	-	6.58	未查	CA125,CA199,CA153	抗血小板+抗凝	-	4
18	69/男	肺腺癌	Ⅳ	2	+	4	MSM	双侧前+后循环	-	17.10	2.04	CA125,CA199,CA153,NSE	抗血小板+抗凝	-	6
19	70/女	子宫内膜癌	III	6	+	1	MSM	双侧前+后循环	B: PCA	2.61	0.23	CA125,CA153,NSE	抗血小板	CI	6

表1

图1

参考文献 39

[1]	Trousseau A. Plegmasia alba dolens. Lectures on clinical medicine[C]. Paris, 1865:281-332.
[2]	Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms[J]. Blood, 2007, 110(6):1723-1729. pmid: 17496204
[3]	Ikushima S, Ono R, Fukuda K, et al. Trousseau's syndrome: cancer-associated thrombosis[J]. Jpn J Clin Oncol, 2016, 46(3):204-208. doi: 10.1093/jjco/hyv165
[4]	Blom J W, Doggen C J, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis[J]. JAMA, 2005, 293(6):715-722. doi: 10.1001/jama.293.6.715
[5]	Grilz E, Konigsbrugge O, Posch F, et al. Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer[J]. Haematologica, 2018, 103(9):1549-1556. doi: 10.3324/haematol.2018.192419 pmid: 29794142
[6]	Navi B B, Iadecola C. Ischemic stroke in cancer patients: a review of an underappreciated pathology[J]. Ann Neurol, 2018, 83(5):873-883. doi: 10.1002/ana.v83.5
[7]	Navi B B, Reiner A S, Kamel H, et al. Arterial thromboembolic events preceding the diagnosis of cancer in older persons[J]. Blood, 2019, 133(8):781-789. doi: 10.1182/blood-2018-06-860874
[8]	De Stefano V. Arterial thrombosis and cancer: the neglected side of the coin of Trousseau syndrome[J]. Haematologica, 2018, 103(9):1419-1421. doi: 10.3324/haematol.2018.197814
[9]	Schwarzbach C J, Fatar M, Eisele P, et al. DWI lesion patterns in cancer-related stroke: specifying the phenotype[J]. Cerebrovasc Dis Extra, 2015, 5(3):139-145. doi: 10.1159/000439549
[10]	Taccone F S, Jeangette S M, Blecic S A. First-ever stroke as initial presentation of systemic cancer[J]. J Stroke Cerebrovasc Dis, 2008, 17(4):169-174. doi: 10.1016/j.jstrokecerebrovasdis.2008.01.007
[11]	Kim S J, Park J H, Lee M J, et al. Clues to occult cancer in patients with ischemic stroke[J]. PLoS One, 2012, 7(9):e44959. doi: 10.1371/journal.pone.0044959
[12]	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(9):666-682.
[13]	Kwon H M, Lee Y S, Bae H J, et al. Homocysteine as a predictor of early neurological deterioration in acute ischemic stroke[J]. Stroke, 2014, 45(3):871-873. doi: 10.1161/STROKEAHA.113.004099
[14]	Mai H, Xia J, Wu Y, et al. Clinical presentation and imaging characteristics of occult lung cancer associated ischemic stroke[J]. J Clin Neurosci, 2015, 22(2):296-302. doi: 10.1016/j.jocn.2014.05.039
[15]	Barnett H, Taylor D W, Haynes R B, et al. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis[J]. N Engl J Med, 1991, 325(7):445-453. doi: 10.1056/NEJM199108153250701
[16]	Bang O Y, Chung J, Lee M J, et al. Cancer-related stroke: an emerging subtype of ischemic stroke with unique pathomechanisms[J]. J Stroke, 2020, 22(1):1-10. doi: 10.5853/jos.2019.02278
[17]	郭琳佳, 虞峰, 陈靖, 等. 恶性肿瘤与非肿瘤患者发生脑梗死的临床与影像特点比较[J]. 中国康复理论与实践, 2018, 24(11):1338-1343.
[18]	Zuo P Y, Chen X L, Liu Y W, et al. Increased risk of cerebrovascular events in patients with cancer treated with bevacizumab: a meta-analysis[J]. PLoS One, 2014, 9(7):e102484. doi: 10.1371/journal.pone.0102484
[19]	Li S H, Chen W H, Tang Y, et al. Incidence of ischemic stroke post-chemotherapy: a retrospective review of 10,963 patients[J]. Clin Neurol Neurosurg, 2006, 108(2):150-156. doi: 10.1016/j.clineuro.2005.03.008
[20]	张晓, 赵媛, 李尧, 等. 以急性多发性脑梗死为表现的Trousseau综合征的临床特征研究[J]. 实用心脑肺血管病杂志, 2018, 26(8):37-42.
[21]	黄刚, 袁敏, 项正兵, 等. 以多发性急性脑梗死为表现的Trousseau综合征临床及影像学特点分析[J]. 中风与神经疾病杂志, 2017, 34(9):797-800.
[22]	国丽茹, 李彦青, 王澜涛, 等. 以多发急性脑梗死为首发表现的Trousseau综合征12例临床分析[J]. 中华全科医师杂志, 2019, 18(5):479-482.
[23]	张璇, 郭文静, 陈菲, 等. Trousseau综合征引起的缺血性脑卒中2例并文献复习[J]. 神经损伤与功能重建, 2019, 14(1):40-42, 52.
[24]	Sanossian N, Djabiras C, Mack W J, et al. Trends in cancer diagnoses among inpatients hospitalized with stroke[J]. J Stroke Cerebrovasc Dis, 2013, 22(7):1146-1150. doi: 10.1016/j.jstrokecerebrovasdis.2012.11.016
[25]	Singhal A B, Topcuoglu M A, Buonanno F S. Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis: a diffusion-weighted magnetic resonance imaging study[J]. Stroke, 2002, 33(5):1267-1273. pmid: 11988602
[26]	Kim S G, Hong J M, Kim H Y, et al. Ischemic stroke in cancer patients with and without conventional mechanisms: a multicenter study in Korea[J]. Stroke, 2010, 41(4):798-801. doi: 10.1161/STROKEAHA.109.571356
[27]	Mochmann H C, Scheitz J F, Petzold G C, et al. Coronary angiographic findings in acute ischemic stroke patients with elevated cardiac troponin: The Troponin Elevation in Acute Ischemic Stroke (TRELAS) Study[J]. Circulation, 2016, 133(13):1264-1271. doi: 10.1161/CIRCULATIONAHA.115.018547
[28]	Thålin C, Demers M, Blomgren B, et al. NETosis promotes cancer-associated arterial microthrombosis presenting as ischemic stroke with troponin elevation[J]. Thromb Res, 2016, 139:56-64. doi: 10.1016/j.thromres.2016.01.009
[29]	Khorana A A, Dalal M, Lin J, et al. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States[J]. Cancer, 2013, 119(3):648-655. doi: 10.1002/cncr.27772
[30]	Thompson C M, Rodgers L R. Analysis of the autopsy records of 157 cases of carcinoma of the pancreas with particular reference to the incidence of thromboembolism[J]. Am J Med Sci, 1952, 223(5):469-478. doi: 10.1097/00000441-195205000-00001
[31]	Iguchi Y, Kimura K, Kobayashi K, et al. Ischaemic stroke with malignancy may often be caused by paradoxical embolism[J]. J Neurol Neurosurg Psychiatry, 2006, 77(12):1336-1339. doi: 10.1136/jnnp.2006.092940
[32]	Umemura T, Yamamoto J, Akiba D, et al. Bilateral cerebral embolism as a characteristic feature of patients with Trousseau syndrome[J]. J Clin Neurosci, 2017, 42:155-159. doi: S0967-5868(17)30101-7 pmid: 28431956
[33]	Ito S, Ueda A, Murate K, et al. Differentiation of cancer from atrial fibrillation in patients with acute multifocal stroke[J]. J Neurol Sci, 2016, 368:344-348. doi: 10.1016/j.jns.2016.07.054
[34]	Jovin T G, Boosupalli V, Zivkovic S A, et al. High titers of CA-125 may be associated with recurrent ischemic strokes in patients with cancer[J]. Neurology, 2005, 64(11):1944-1945. pmid: 15955949
[35]	Gon Y, Sakaguchi M, Takasugi J, et al. Plasma D-dimer levels and ischaemic lesions in multiple vascular regions can predict occult cancer in patients with cryptogenic stroke[J]. Eur J Neurol, 2017, 24(3):503-508. doi: 10.1111/ene.13234 pmid: 28026909
[36]	Navi B B, Singer S, Merkler A E, et al. Recurrent thromboembolic events after ischemic stroke in patients with cancer[J]. Neurology, 2014, 83(1):26-33. doi: 10.1212/WNL.0000000000000539
[37]	Li N. Platelets in cancer metastasis: To help the "villain" to do evil[J]. Int J Cancer, 2016, 138(9):2078-2087. doi: 10.1002/ijc.v138.9
[38]	Nam K W, Kim C K, Kim T J, et al. Treatment of cryptogenic stroke with active cancer with a new oral anticoagulant[J]. J Stroke Cerebrovasc Dis, 2017, 26(12):2976-2980. doi: 10.1016/j.jstrokecerebrovasdis.2017.07.029
[39]	Navi B B, Marshall R S, Bobrow D, et al. Enoxaparin vs aspirin in patients with cancer and ischemic stroke: The TEACH pilot randomized clinical trial[J]. JAMA Neurol, 2018, 75(3):379-381. doi: 10.1001/jamaneurol.2017.4211