Research status of progressive ischemic stroke_West China Medical Journal

Authors：

JING Lijun ¹ , YANG Jingchen ² ,  YANG Weimin ¹

1. Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China;
2. Department of Clinical Medicine, College of Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P. R. China;

Corresponding author：

YANG Weimin, Email: weiminyanghn@163.com

Keywords：

Progressive ischemic stroke; Pathogenesis; Influencing factors; Predictive indicators

DOI：

10.7507/1002-0179.202005070

Video：

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Progressive ischemic stroke is one of the major diseases damaging the health of Chinese people. Its pathogenesis is complex and there are many influencing factors, but the treatment methods are limited. In recent years, the rapid development of neuroimaging and the results of various clinical trials have been reported in succession, which have made new progress in the clinical diagnosis and treatment of progressive ischemic stroke. This paper summarizes the progress of progressive ischemic stroke, introduces its pathogenesis (including increased intracranial pressure and reduced perfusion pressure, thrombosis progression, hemorrhagic transformation, cerebral edema, and inflammatory response), influencing factors, predictive indicators (including image indicators, biochemical indicators, and molecular biology indicators) and treatment (including admission to “stroke unit”, intravascular treatment, platelet aggregation inhibition treatment, anticoagulation treatment, and general treatment), to provide references for preventing the occurrence and development of progressive ischemic stroke, assessing the condition, guiding treatment and improving the prognosis.

Citation： JING Lijun, YANG Jingchen, YANG Weimin. Research status of progressive ischemic stroke. West China Medical Journal, 2020, 35(6): 646-651. doi: 10.7507/1002-0179.202005070 Copy

1.	Zhou M, Wang H, Zhu J, et al. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the global burden of disease study 2013. Lancet, 2016, 387(10015): 251-272.
2.	GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol, 2019, 18(5): 439-458.
3.	GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the global burden of disease study 2016. Lancet, 2017, 390(10100): 1151-1210.
4.	Chao BH, Yan F, Hua Y, et al. Stroke prevention and control system in China: CSPPC-stroke program. Int J Stroke, 2020, 33: 712.
5.	Wu Y, Wang X, Zhou X, et al. Temporal expression of apelin/apelin receptor in ischemic stroke and its therapeutic potential. Front Mol Neurosci, 2017, 10(1): 1062-1068.
6.	Li H, Dai Y, Wu H, et al. Predictors of early neurologic deterioration in acute pontine infarction. Stroke, 2020, 51(2): 637-640.
7.	Duan Z, Guo W, Tang T, et al. Relationship between high-sensitivity C-reactive protein and early neurological deterioration in stroke patients with and without atrial fibrillation. Heart Lung, 2020, 49(2): 193-197.
8.	Helleberg BH, Ellekjaer H, Rohweder G, et al. Mechanisms, predictors and clinical impact of early neurological deterioration: the protocol of the trondheim early neurological deterioration study. BMC Neurol, 2014, 14: 201.
9.	Seners P, Baron JC. Revisiting “progressive stroke”: incidence, predictors, pathophysiology, and management of unexplained early neurological deterioration following acute ischemic stroke. J Neurol, 2018, 265(1): 216-225.
10.	Hart RG, Pearce LA, Bakheet MF, et al. Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial. J Stroke Cerebrovasc Dis, 2014, 23(4): 618-624.
11.	Birschel P, Ellul J, Barer D. Progressing stroke: towards an internationally agreed definition. Cerebrovasc Dis, 2004, 17(2/3): 242-252.
12.	Stone JA, Willey JZ, Keyrouz S, et al. Therapies for hemorrhagic transformation in acute ischemic stroke. Curr Treat Options Neurol, 2017, 19(1): 1-15.
13.	Seners P, Turc G, Oppenheim C, et al. Incidence, causes and predictors of neurological deterioration occurring within 24 h following acute ischaemic stroke: a systematic review with pathophysiological implications. J Neurol Neurosurg Psychiatry, 2015, 86(1): 87-94.
14.	Saver JL, Altman H. Relationship between neurologic deficit severity and final functional outcome shifts and strengthens during first hours after onset. Stroke, 2012, 43(6): 1537-1541.
15.	杨磊, 胡文立. 应该规范进展性卒中的定义. 中华神经科杂志, 2011, 44(4): 292-293.
16.	Beard DJ, McLeod DD, Logan CL, et al. Intracranial pressure elevation reduces flow through collateral vessels and the penetrating arterioles they supply. A possible explanation for “collateral failure” and infarct expansion after ischemic stroke. J Cereb Blood Flow Metab, 2015, 35(5): 861-872.
17.	Sharma VK, Tan BQ, Ngiam NJ, et al. Abstract WP243: randomized clinical trial evaluating the safety and feasibility of intensive lowering of blood pressure in acute ischemic stroke patients treated with intravenous thrombolysis and assessed using CT perfusion imaging. Stroke, 2019, 50(Suppl 1): AWP243.
18.	Mistry EA, Mehta T, Mistry A, et al. Blood pressure variability and neurologic outcome after endovascular thrombectomy a secondary analysis of the BEST study. Stroke, 2020, 51(2): 511-518.
19.	Cuadrado-Godia E, Jimena S, Ois A, et al. Factors associated with early outcome in patients with large-vessel carotid strokes. J Neurol Neurosurg Psychiatry, 2013, 84(3): 305-309.
20.	Seners P, Hurford R, Tisserand M, et al. Is unexplained early neurological deterioration after intravenous thrombolysis associated with thrombus extension?. Stroke, 2017, 48(2): 348-352.
21.	Kim JM, Bae JH, Park KY, et al. Incidence and mechanism of early neurological deterioration after endovascular thrombectomy. J Neurol, 2019, 266(3): 609-615.
22.	Thanvi B, Treadwell S, Robinson T. Early neurological deterioration in acute ischaemic stroke: predictors, mechanisms and management. Postgrad Med J, 2008, 84(994): 412-417.
23.	Elsaid N, Mustafa W, Saied A. Radiological predictors of hemorrhagic transformation after acute ischemic stroke: an evidence-based analysis. Neuroradiol J, 2020, 33(2): 118-133.
24.	Folsom AR, Tang W, George KM, et al. Prospective study ofγ’ fibrinogen and incident venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Thromb Res, 2016, 139: 44-49.
25.	Zhang X, Wang A, Zhang J, et al. Association of plasma C-reactive protein with ischaemic stroke: a mendelian randomization study. Eur J Neurol, 2019, 27(3): 565-571.
26.	Lee SJ, Hong JM, Lee SE, et al. Association of fibrinogen level with early neurological deterioration among acute ischemic stroke patients with diabetes. BMC Neurol, 2017, 17(1): 101-107.
27.	Bugntcourt JM, Roussel B, GarciaPY, et al. Aspirin non-responder status and early neurological deterioration: a prospective study. Clin Neurol Neurosurg, 2011, 113(3): 196-201.
28.	Chung JW, Kim N, Kang J, et al. Bloodpressure variability and the development of early neurological deterioration following acute ischemic stroke. J Hypertens, 2015, 33(10): 2099-2106.
29.	Zhang J, Yang Y, Sun H, et al. Hemorrhagic transformation after cerebral infarction: current concepts and challenges. AnnTransl Med, 2014, 2(8): 81.
30.	Best LM, Webb AC, Gurusamy KS, et al. Transcranial doppler ultrasound detection of microemboli as a predictor of cerebral events in patients with symptomatic and asymptomatic carotid disease: a systematic review and meta-analysis. Eur J Vasc Endovasc Surg, 2016, 52(5): 565-580.
31.	Liu D, Sun W, Scalzo F, et al. Early magnetic resonance imaging predicts early neurological deterioration in acute middle cerebral artery minor stroke. J Stroke Cerebrovasc Dis, 2016, 25(2): 469-474.
32.	Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
33.	Simonsen CZ, Schmitz ML, Madsen MH, et al. Early neurological deterioration after thrombolysis: clinical and imaging predictors. Int J Stroke, 2016, 11(7): 776-782.
34.	Jiang J, Huang X, Zhang Y, et al. Total MRI burden of cerebral vessel disease correlates with the progression in patients with acute single small subcortical strokes. Brain Behav, 2019, 9(1): e01173.
35.	Dávalos A, Toni D, Iwein F, et al. Neurological deterioration in acute ischemic stroke: potential predictors and associated factors in the European Cooperative Acute Stroke Study (ECASS) Ⅰ. Stroke, 1999, 30(12): 2631-2636.
36.	Huang Y, Wang JG, Wei JW, et al. Age and gender variations in the management of ischaemic stroke in China. Int J Stroke, 2010, 5(5): 351-359.
37.	Martin AJ, Price CI. A systematic review and meta-analysis of molecular biomarkers associated with early neurological deterioration following acute stroke. Cerebrovasc Dis, 2018, 46(5/6): 230-241.
38.	Bhatia K, Mohanty S, Tripathi BK, et al. Predictors of early neurological deterioration in patients with acute ischaemic stroke with special reference to blood urea nitrogen (BUN)/creatinine ratio & urine specific gravity. Indian J Med Res, 2015, 141(3): 299-307.
39.	潘杨, 张丽. 脂蛋白相关磷脂酶A2与轻型缺血性卒中早期神经功能恶化风险分层的相关性研究. 南京医科大学学报(自然科学版), 2016, 36(8): 991-994.
40.	Maiolino G, Bisogni V, Rossitto G, et al. Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications. World J Cardiol, 2015, 7(10): 609-620.
41.	Yi X, Zhou Q, Sui G, et al. Matrix metalloproteinase-9 gene polymorphisms are associated with ischemic stroke severity and early neurologic deterioration in patients with atrial fibrillation. Brain Behav, 2019, 9(6): e01291.
42.	Mirzaei H, Momeni F, Saadatpour L, et al. MicroRNA: relevance to stroke diagnosis, prognosis, and therapy. J Cell Physiol, 2018, 233(2): 856-865.
43.	Ungerge MN, Ringleb P, Reuter B, et al. Stroke unit admission is associated with better outcome and lower mortality in patients with intracerebral hemorrhage. Eur J Neurol, 2020, 27(5): 825-832.
44.	Jayaraman MV, Hussain MS, Abruzzo T, et al. Embolectomy for stroke with emergent large vesselocclusion (ELVO): report ofthe standards and guidelines committee of the society of neurointerventional surgery. J Neurointerv Surg, 2015, 7(5): 316-321.
45.	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. 中华神经科杂志, 2018, 51(9): 666-682.
46.	Berkhemer OA, Fransen PSS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med, 2015, 372(1): 11-20.
47.	Powers WJ, Rabinstein AA, Ackerson T, et al. Correction to: guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke. Stroke, 2019, 50(12): e440-e441.
48.	Yi X, Chi W, Wang C, et al. Low-molecular weightheparin or dual antiplatelet therapy is more effective than aspirin alone in preventing early neurological deterioration and improving the 6-month outcome in ischemic stroke patients. J Clin Neurol, 2015, 11(1): 57-65.
49.	Seiffge DJ, Werring DJ, Paciaroni M, et al. Timing of anticoagulation after recent ischaemic stroke in patients with atrial flbrillation. Lancet Neurol, 2019, 18(1): 117-126.
50.	李知静, 金香兰. 急性缺血性脑卒中氧治疗的研究进展. 医学综述, 2020, 26(2): 306-310.

1. Zhou M, Wang H, Zhu J, et al. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the global burden of disease study 2013. Lancet, 2016, 387(10015): 251-272.
2. GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol, 2019, 18(5): 439-458.
3. GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the global burden of disease study 2016. Lancet, 2017, 390(10100): 1151-1210.
4. Chao BH, Yan F, Hua Y, et al. Stroke prevention and control system in China: CSPPC-stroke program. Int J Stroke, 2020, 33: 712.
5. Wu Y, Wang X, Zhou X, et al. Temporal expression of apelin/apelin receptor in ischemic stroke and its therapeutic potential. Front Mol Neurosci, 2017, 10(1): 1062-1068.
6. Li H, Dai Y, Wu H, et al. Predictors of early neurologic deterioration in acute pontine infarction. Stroke, 2020, 51(2): 637-640.
7. Duan Z, Guo W, Tang T, et al. Relationship between high-sensitivity C-reactive protein and early neurological deterioration in stroke patients with and without atrial fibrillation. Heart Lung, 2020, 49(2): 193-197.
8. Helleberg BH, Ellekjaer H, Rohweder G, et al. Mechanisms, predictors and clinical impact of early neurological deterioration: the protocol of the trondheim early neurological deterioration study. BMC Neurol, 2014, 14: 201.
9. Seners P, Baron JC. Revisiting “progressive stroke”: incidence, predictors, pathophysiology, and management of unexplained early neurological deterioration following acute ischemic stroke. J Neurol, 2018, 265(1): 216-225.
10. Hart RG, Pearce LA, Bakheet MF, et al. Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial. J Stroke Cerebrovasc Dis, 2014, 23(4): 618-624.
11. Birschel P, Ellul J, Barer D. Progressing stroke: towards an internationally agreed definition. Cerebrovasc Dis, 2004, 17(2/3): 242-252.
12. Stone JA, Willey JZ, Keyrouz S, et al. Therapies for hemorrhagic transformation in acute ischemic stroke. Curr Treat Options Neurol, 2017, 19(1): 1-15.
13. Seners P, Turc G, Oppenheim C, et al. Incidence, causes and predictors of neurological deterioration occurring within 24 h following acute ischaemic stroke: a systematic review with pathophysiological implications. J Neurol Neurosurg Psychiatry, 2015, 86(1): 87-94.
14. Saver JL, Altman H. Relationship between neurologic deficit severity and final functional outcome shifts and strengthens during first hours after onset. Stroke, 2012, 43(6): 1537-1541.
15. 杨磊, 胡文立. 应该规范进展性卒中的定义. 中华神经科杂志, 2011, 44(4): 292-293.
16. Beard DJ, McLeod DD, Logan CL, et al. Intracranial pressure elevation reduces flow through collateral vessels and the penetrating arterioles they supply. A possible explanation for “collateral failure” and infarct expansion after ischemic stroke. J Cereb Blood Flow Metab, 2015, 35(5): 861-872.
17. Sharma VK, Tan BQ, Ngiam NJ, et al. Abstract WP243: randomized clinical trial evaluating the safety and feasibility of intensive lowering of blood pressure in acute ischemic stroke patients treated with intravenous thrombolysis and assessed using CT perfusion imaging. Stroke, 2019, 50(Suppl 1): AWP243.
18. Mistry EA, Mehta T, Mistry A, et al. Blood pressure variability and neurologic outcome after endovascular thrombectomy a secondary analysis of the BEST study. Stroke, 2020, 51(2): 511-518.
19. Cuadrado-Godia E, Jimena S, Ois A, et al. Factors associated with early outcome in patients with large-vessel carotid strokes. J Neurol Neurosurg Psychiatry, 2013, 84(3): 305-309.
20. Seners P, Hurford R, Tisserand M, et al. Is unexplained early neurological deterioration after intravenous thrombolysis associated with thrombus extension?. Stroke, 2017, 48(2): 348-352.
21. Kim JM, Bae JH, Park KY, et al. Incidence and mechanism of early neurological deterioration after endovascular thrombectomy. J Neurol, 2019, 266(3): 609-615.
22. Thanvi B, Treadwell S, Robinson T. Early neurological deterioration in acute ischaemic stroke: predictors, mechanisms and management. Postgrad Med J, 2008, 84(994): 412-417.
23. Elsaid N, Mustafa W, Saied A. Radiological predictors of hemorrhagic transformation after acute ischemic stroke: an evidence-based analysis. Neuroradiol J, 2020, 33(2): 118-133.
24. Folsom AR, Tang W, George KM, et al. Prospective study ofγ’ fibrinogen and incident venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Thromb Res, 2016, 139: 44-49.
25. Zhang X, Wang A, Zhang J, et al. Association of plasma C-reactive protein with ischaemic stroke: a mendelian randomization study. Eur J Neurol, 2019, 27(3): 565-571.
26. Lee SJ, Hong JM, Lee SE, et al. Association of fibrinogen level with early neurological deterioration among acute ischemic stroke patients with diabetes. BMC Neurol, 2017, 17(1): 101-107.
27. Bugntcourt JM, Roussel B, GarciaPY, et al. Aspirin non-responder status and early neurological deterioration: a prospective study. Clin Neurol Neurosurg, 2011, 113(3): 196-201.
28. Chung JW, Kim N, Kang J, et al. Bloodpressure variability and the development of early neurological deterioration following acute ischemic stroke. J Hypertens, 2015, 33(10): 2099-2106.
29. Zhang J, Yang Y, Sun H, et al. Hemorrhagic transformation after cerebral infarction: current concepts and challenges. AnnTransl Med, 2014, 2(8): 81.
30. Best LM, Webb AC, Gurusamy KS, et al. Transcranial doppler ultrasound detection of microemboli as a predictor of cerebral events in patients with symptomatic and asymptomatic carotid disease: a systematic review and meta-analysis. Eur J Vasc Endovasc Surg, 2016, 52(5): 565-580.
31. Liu D, Sun W, Scalzo F, et al. Early magnetic resonance imaging predicts early neurological deterioration in acute middle cerebral artery minor stroke. J Stroke Cerebrovasc Dis, 2016, 25(2): 469-474.
32. Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
33. Simonsen CZ, Schmitz ML, Madsen MH, et al. Early neurological deterioration after thrombolysis: clinical and imaging predictors. Int J Stroke, 2016, 11(7): 776-782.
34. Jiang J, Huang X, Zhang Y, et al. Total MRI burden of cerebral vessel disease correlates with the progression in patients with acute single small subcortical strokes. Brain Behav, 2019, 9(1): e01173.
35. Dávalos A, Toni D, Iwein F, et al. Neurological deterioration in acute ischemic stroke: potential predictors and associated factors in the European Cooperative Acute Stroke Study (ECASS) Ⅰ. Stroke, 1999, 30(12): 2631-2636.
36. Huang Y, Wang JG, Wei JW, et al. Age and gender variations in the management of ischaemic stroke in China. Int J Stroke, 2010, 5(5): 351-359.
37. Martin AJ, Price CI. A systematic review and meta-analysis of molecular biomarkers associated with early neurological deterioration following acute stroke. Cerebrovasc Dis, 2018, 46(5/6): 230-241.
38. Bhatia K, Mohanty S, Tripathi BK, et al. Predictors of early neurological deterioration in patients with acute ischaemic stroke with special reference to blood urea nitrogen (BUN)/creatinine ratio & urine specific gravity. Indian J Med Res, 2015, 141(3): 299-307.
39. 潘杨, 张丽. 脂蛋白相关磷脂酶A2与轻型缺血性卒中早期神经功能恶化风险分层的相关性研究. 南京医科大学学报(自然科学版), 2016, 36(8): 991-994.
40. Maiolino G, Bisogni V, Rossitto G, et al. Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications. World J Cardiol, 2015, 7(10): 609-620.
41. Yi X, Zhou Q, Sui G, et al. Matrix metalloproteinase-9 gene polymorphisms are associated with ischemic stroke severity and early neurologic deterioration in patients with atrial fibrillation. Brain Behav, 2019, 9(6): e01291.
42. Mirzaei H, Momeni F, Saadatpour L, et al. MicroRNA: relevance to stroke diagnosis, prognosis, and therapy. J Cell Physiol, 2018, 233(2): 856-865.
43. Ungerge MN, Ringleb P, Reuter B, et al. Stroke unit admission is associated with better outcome and lower mortality in patients with intracerebral hemorrhage. Eur J Neurol, 2020, 27(5): 825-832.
44. Jayaraman MV, Hussain MS, Abruzzo T, et al. Embolectomy for stroke with emergent large vesselocclusion (ELVO): report ofthe standards and guidelines committee of the society of neurointerventional surgery. J Neurointerv Surg, 2015, 7(5): 316-321.
45. 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. 中华神经科杂志, 2018, 51(9): 666-682.
46. Berkhemer OA, Fransen PSS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med, 2015, 372(1): 11-20.
47. Powers WJ, Rabinstein AA, Ackerson T, et al. Correction to: guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke. Stroke, 2019, 50(12): e440-e441.
48. Yi X, Chi W, Wang C, et al. Low-molecular weightheparin or dual antiplatelet therapy is more effective than aspirin alone in preventing early neurological deterioration and improving the 6-month outcome in ischemic stroke patients. J Clin Neurol, 2015, 11(1): 57-65.
49. Seiffge DJ, Werring DJ, Paciaroni M, et al. Timing of anticoagulation after recent ischaemic stroke in patients with atrial flbrillation. Lancet Neurol, 2019, 18(1): 117-126.
50. 李知静, 金香兰. 急性缺血性脑卒中氧治疗的研究进展. 医学综述, 2020, 26(2): 306-310.

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