Research Progress on the Pathogenesis of Cancer-Associated Ischemic Stroke

doi:10.3969/j.issn.1673-5765.2025.02.002

Abstract

Abstract: Cancer-associated ischemic stroke (CAIS) is a common and complex complication in tumor patients, manifesting as multi-site thrombosis and multiple cerebral infarctions. Its pathogenesis is very complicated. This article reviewed the pathogenesis of CAIS, including the direct effects of tumors, hypercoagulabale state, nonbacterial thrombotic endocarditis, and tumor-related examinations or treatments, aiming to provide references for the formulation of individualized anti-cancer and stroke prevention strategies for tumor patients.

Key words: Cancer-associated ischemic stroke; Pathogenesis; Research progress

摘要： 肿瘤相关性缺血性卒中是肿瘤患者常见且复杂的并发症，表现为多部位血栓形成和多发性脑梗死，其发病机制非常复杂。本文对肿瘤直接作用、高凝状态、非细菌性血栓性心内膜炎、肿瘤相关检查或治疗等肿瘤相关性缺血性卒中的发病机制进行了综述，以期为肿瘤患者制订个体化抗癌和卒中预防策略提供参考。

关键词: 肿瘤相关性缺血性卒中; 发病机制; 研究进展

CLC Number:

WANG Shuhong, XU Bingdong, LIN Yingze, YANG Danping, ZHANG Yusheng. Research Progress on the Pathogenesis of Cancer-Associated Ischemic Stroke[J]. Chinese Journal of Stroke, 2025, 20(2): 138-143.

王舒泓, 徐炳东, 林英泽, 杨丹萍, 张玉生. 肿瘤相关性缺血性卒中的发病机制研究进展[J]. 中国卒中杂志, 2025, 20(2): 138-143.

References

[1] HSU J Y，LIU A B. Anticoagulants for cancer-associated ischemic stroke[J]. Tzu Chi Med J，2019，31（3）：144-148.
[2] 张楚楚，张蓓，郭甜甜，等. 特鲁索综合征的研究进展[J]. 临床医学进展，2024，14（2）：2420-2425.
ZHANG C C，ZHANG B，GUO T T，et al. Trousseau’s syndrome research progress[J]. Advances in Clinical Medicine，2024，14（2）：2420-2425.
[3] GBD 2019 Stroke Collaborators. Global，regional，and national burden of stroke and its risk factors，1990—2019：a systematic analysis for the global burden of disease study 2019[J]. Lancet Neurol，2021，20（10）：795-820.
[4] LEE K P，HUANG H C，TSAI J Y，et al. Effects of cancer on stroke recurrence and mortality：a single-center retrospective cohort study[J/OL]. eNeurologicalSci，2023，32：100474[2024-12-10]. https://doi.org/10.1016/j.ensci. 2023.100474.
[5] TURNER M，MURCHIE P，DERBY S，et al. Is stroke incidence increased in survivors of adult cancers？A systematic review and meta-analysis[J]. J Cancer Surviv，2022，16（6）：1414-1448.
[6] European Association for the Study of the Liver. EASL clinical practice guidelines：management of hepatocellular carcinoma[J]. J Hepatol，2018，69（1）：182-236.
[7] ZWICKER J I，LIEBMAN H A，NEUBERG D，et al. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy[J]. Clin Cancer Res，2009，15（22）：6830-6840.
[8] SUN B B，FAN S Y，LI Z F，et al. Clinical and neuroimaging features of acute ischemic stroke in cancer patients[J]. Eur Neurol，2016，75（5/6）：292-299.
[9] FONKEM E，DAYAWANSA S，STROBERG E，et al. Neurological presentations of intravascular lymphoma（IVL）：meta-analysis of 654 patients[J/OL]. BMC Neurol，2016，16：9[2024-12-10]. https://doi.org/10.1186/s12883-015-0509-8.
[10] HAJJO R，SABBAH D A，BARDAWEEL S K，et al. Identification of tumor-specific MRI biomarkers using machine learning（ML）[J/OL]. Diagnostics（Basel），2021，11（5）：742[2024-12-10]. https://doi.org/10.3390/diagnostics11050742.
[11] MA Y G，YANG X Y，CHATTERJEE V，et al. Role of neutrophil extracellular traps and vesicles in regulating vascular endothelial permeability[J/OL]. Front Immunol，2019，10：1037[2024-12-10]. https://doi.org/10.3389/fimmu.2019.01037.
[12] SHAO B Z，YAO Y，LI J P，et al. The role of neutrophil extracellular traps in cancer[J/OL]. Front Oncol，2021，11：714357[2024-12-10]. https://doi.org/10.3389/fonc. 2021.714357.
[13] SUZUKI-INOUE K. Platelets and cancer-associated thrombosis：focusing on the platelet activation receptor CLEC-2 and podoplanin[J]. Blood，2019，134（22）：1912-1918.
[14] HISADA Y，MACKMAN N. Cancer-associated pathways and biomarkers of venous thrombosis[J]. Blood，2017，130（13）：1499-1506.
[15] DIXIT S，MAHAKALKAR C，KSHIRSAGAR S，et al. Exploring the prognostic role of D-dimer levels in pancreatic cancer：a comprehensive review of clinicopathological associations[J/OL]. Cureus，2024，16（9）：e68627[2024-12-10]. https://doi.org/10.7759/cureus.68627.
[16] NAVI B B，REINER A S，KAMEL H，et al. Association between incident cancer and subsequent stroke[J]. Ann Neurol，2015，77（2）：291-300.
[17] PALACIOS-ACEDO A L，LANGIU M，CRESCENCE L，et al. Platelet and cancer-cell interactions modulate cancer-associated thrombosis risk in different cancer types[J/OL]. Cancers（Basel），2022，14（3）：730[2024-12-10]. https://doi.org/10.3390/cancers14030730.
[18] HURRELL H，ROBERTS-THOMSON R，PRENDERGAST B D. Non-infective endocarditis[J]. Heart，2020，106（13）：1023-1029.
[19] SANTARPINO G，LOFRUMENTO F，ZITO C，et al. Exploring the complexities of non-bacterial thrombotic endocarditis：highlights from literature and case studies[J/OL]. J Clin Med，2024，13（16）：4904[2024-12-10]. https://doi.org/10.3390/jcm13164904.
[20] AL CHALABY S，MAKHIJA R R，SHARMA A N，et al. Nonbacterial thrombotic endocarditis：presentation，pathophysiology，diagnosis and management[J/OL]. Rev Cardiovasc Med，2022，23（4）：137[2024-12-10].
https://doi.org/10.31083/j.rcm2304137.
[21] FERLAN G，FIORELLA A，DE PASQUALE C，et al. Primary coronary embolism as an unusual manifestation of nonbacterial thrombotic endocarditis in a patient with gastric cancer[J/OL]. Cardiol Res Pract，2010，2010：319732[2024-12-10]. https://doi.org/10.4061/2010/319732.
[22] SANTIAGO L E，KUJUNDZIC W，WONG S，et al. An unusual case of nonbacterial thrombotic endocarditis attributable to malignancy[J/OL]. Cureus，2023，15（9）：e44734[2024-12-10]. https://doi.org/10.7759/cureus.44734.
[23] YOO J，CHOI J K，KIM Y D，et al. Outcome of stroke patients with cancer and nonbacterial thrombotic endocarditis[J]. J Stroke，2020，22（2）：245-253.
[24] LYMAN G H，KHORANA A A，KUDERER N M，et al. Cancer and thrombosis：back to the future renewed interest in an old problem[J]. Cancer Invest，2009，27（5）：472-473.
[25] JONES O M，REES M，JOHN T G，et al. Biopsy of resectable colorectal liver metastases causes tumour dissemination and adversely affects survival after liver resection[J]. Br J Surg，2005，92（9）：1165-1168.
[26] HUANG S T，YU T M，CHEN C H，et al. Risk of major cardiovascular disease after exposure to contrast media：a nationwide population-based cohort study on dialysis patients[J/OL]. Metabolites，2023，13（2）：266[2024-12-10]. https://doi.org/10.3390/metabo13020266.
[27] KOCH M，ANTOLOVIC D，KIENLE P，et al. Increased detection rate and potential prognostic impact of disseminated tumor cells in patients undergoing endorectal ultrasound for rectal cancer[J]. Int J Colorectal Dis，2007，22（4）：359-365.
[28] MA Y T，KROEMER G. The cancer-immune dialogue in the context of stress[J]. Nat Rev Immunol，2024，24（4）：264-281.
[29] CAMPIA U. Vascular effects of cancer treatments[J]. Vasc Med，2020，25（3）：226-234.
[30] SANO N，SATOW T，MARUYAMA D，et al. Relationship between histologic features and outcomes of carotid revascularization for radiation-induced stenosis[J]. J Vasc Surg，2015，62（2）：370-377.
[31] WOOCK M，MARTINEZ-MAJANDER N，SEIFFGE D J，et al. Cancer and stroke：commonly encountered by clinicians，but little evidence to guide clinical approach[J/OL]. Ther Adv Neurol Disord，2022，15：17562864221106362[2024-12-10]. https://doi.org/10.1177/17562864221106362.
[32] QUARTERMAINE C，GHAZI S M，YASIN A，et al. Cardiovascular toxicities of BTK inhibitors in chronic lymphocytic leukemia[J]. JACC CardioOncol，2023，5（5）：570-590.
[33] JAIN P，GUTIERREZ BUGARIN J，GUHA A，et al. Cardiovascular adverse events are associated with usage of immune checkpoint inhibitors in real-world clinical data across the United States[J/OL]. ESMO Open，2021，6（5）：100252[2024-12-10]. https://doi.org/10.1016/j.esmoop.2021.100252.
[34] MOIK F，CHAN W E，WIEDEMANN S，et al. Incidence，risk factors，and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy[J]. Blood，2021，137（12）：1669-1678.
[35] MANQUAT E，RAVAUX H，KINDERMANS M，et al. Impact of impaired cerebral blood flow autoregulation on electroencephalogram signals in adults undergoing propofol anaesthesia：a pilot study[J/OL]. BJA Open，2022，1：100004[2024-12-10]. https://doi.org/10.1016/j.bjao.2022.100004.
[36] YAO J X，LI S，CUI Q Y，et al. Intraoperative hypotension and postoperative stroke in older patients who had brain tumor resections：a retrospective cohort analysis[J/OL]. World Neurosurg，2023，174：e72-e81[2024-12-10]. https://doi.org/10.1016/j.wneu.2023.02.136.
[37] FAN J L，NOGUEIRA R C，BRASSARD P，et al. Integrative physiological assessment of cerebral hemodynamics and metabolism in acute ischemic stroke[J]. J Cereb Blood Flow Metab，2022，42（3）：454-470.
[38] WALL T P，BUGGY D J. Perioperative intravenous lidocaine and metastatic cancer recurrence—a narrative review[J/OL]. Front Oncol，2021，11：688896[2024-12-10]. https://doi.org/10.3389/fonc.2021.688896.
[39] WU J，LU A D，ZHANG L P，et al. Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia[J]. Chin J Hematol，2019，40（1）：52-57.