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Neurotherapeutics
Published in: Neurotherapeutics 3/2023

01-04-2023 | Stroke | Review

Hemorrhagic Conversion of Acute Ischemic Stroke

Authors: Adeel S. Zubair, Kevin N. Sheth

Published in: Neurotherapeutics | Issue 3/2023

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Abstract

Stroke is a leading cause of morbidity and mortality worldwide; a serious complication of ischemic stroke is hemorrhagic transformation. Current treatment of acute ischemic stroke includes endovascular thrombectomy and thrombolytic therapy. Both of these treatment options are linked with increased risks of hemorrhagic conversion. The diagnosis and timely management of patients with hemorrhagic conversion is critically important to patient outcomes. This review aims to discuss hemorrhagic conversion of acute ischemic stroke including discussion of the pathophysiology, review of risk factors, imaging considerations, and treatment of patients with hemorrhagic conversion.
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Literature
1.
Zubair AS, Sheth KN. Emergency care of patients with acute ischemic stroke. Neurol Clin. 2021;39(2):391–404.PubMedCrossRef
2.
3.
Krishnamurthi RV, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health. 2013;1(5):e259–81.PubMedPubMedCentralCrossRef
4.
Lodder J, Krijne-Kubat B, Broekman J. Cerebral hemorrhagic infarction at autopsy: cardiac embolic cause and the relationship to the cause of death. Stroke. 1986;17(4):626–9.PubMedCrossRef
5.
6.
England TJ, et al. Asymptomatic hemorrhagic transformation of infarction and its relationship with functional outcome and stroke subtype: assessment from the Tinzaparin in Acute Ischaemic Stroke Trial. Stroke. 2010;41(12):2834–9.PubMedCrossRef
7.
8.
Benjamin EJ, et al. Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–528.PubMedCrossRef
9.
Miller DJ, Simpson JR, Silver B. Safety of thrombolysis in acute ischemic stroke: a review of complications, risk factors, and newer technologies. Neurohospitalist. 2011;1(3):138–47.PubMedPubMedCentralCrossRef
10.
Whiteley WN, et al. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. Lancet Neurol. 2016;15(9):925–33.PubMedCrossRef
11.
Thiebaut AM, et al. The role of plasminogen activators in stroke treatment: fibrinolysis and beyond. Lancet Neurol. 2018;17(12):1121–32.PubMedCrossRef
12.
Warach SJ, et al. Abstract 43: Comparative effectiveness of routine tenecteplase thrombolysis in acute stroke compared with alteplase: an INternational Collaboration (CERTAIN Collaboration): rates of symptomatic intracranial hemorrhage. Stroke. 2022;53(Suppl_1):A43–A43.CrossRef
13.
Goyal M, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723–31.PubMedCrossRef
14.
Berkhemer OA, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11–20.PubMedCrossRef
15.
Goyal M, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019–30.PubMedCrossRef
16.
Saver JL, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372(24):2285–95.PubMedCrossRef
17.
Campbell BC, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009–18.PubMedCrossRef
18.
19.
Nogueira RG, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11–21.PubMedCrossRef
20.
Balami JS, et al. Neurological complications of acute ischaemic stroke. Lancet Neurol. 2011;10(4):357–71.PubMedCrossRef
21.
van Kranendonk KR, et al. Added prognostic value of hemorrhagic transformation quantification in patients with acute ischemic stroke. Front Neurol. 2020;11:582767.PubMedPubMedCentralCrossRef
22.
Henning EC, et al. Reperfusion-associated hemorrhagic transformation in SHR rats: evidence of symptomatic parenchymal hematoma. Stroke. 2008;39(12):3405–10.PubMedPubMedCentralCrossRef
23.
Arba F, et al. Blood-brain barrier leakage and hemorrhagic transformation: the Reperfusion Injury in Ischemic StroKe (RISK) study. Eur J Neurol. 2021;28(9):3147–54.PubMedCrossRef
24.
Berger C, et al. Hemorrhagic transformation of ischemic brain tissue: asymptomatic or symptomatic? Stroke. 2001;32(6):1330–5.PubMedCrossRef
25.
Jensen M, et al. Clinical characteristics and outcome of patients with hemorrhagic transformation after intravenous thrombolysis in the WAKE-UP trial. Front Neurol. 2020;11:957.PubMedPubMedCentralCrossRef
26.
Iwamoto T, et al. Predicting hemorrhagic transformation after large vessel occlusion stroke in the era of mechanical thrombectomy. PLoS ONE. 2021;16(8):e0256170.PubMedPubMedCentralCrossRef
27.
Boisseau W, et al. Predictors of parenchymal hematoma after mechanical thrombectomy: a multicenter study. Stroke. 2019;50(9):2364–70.PubMedCrossRef
28.
29.
30.
Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS. 2020;17(1):69.PubMedPubMedCentralCrossRef
31.
Lochhead JJ, et al. Structure, function, and regulation of the blood-brain barrier tight junction in central nervous system disorders. Front Physiol. 2020;11:914.PubMedPubMedCentralCrossRef
32.
Bell AH, et al. The neurovascular unit: effects of brain insults during the perinatal period. Front Neurosci. 2019;13:1452.PubMedCrossRef
33.
34.
Arba F, et al. Blood-brain barrier disruption and hemorrhagic transformation in acute ischemic stroke: systematic review and meta-analysis. Front Neurol. 2020;11:594613.PubMedCrossRef
35.
Bernardo-Castro S, et al. Pathophysiology of blood-brain barrier permeability throughout the different stages of ischemic stroke and its implication on hemorrhagic transformation and recovery. Front Neurol. 2020;11:594672.PubMedPubMedCentralCrossRef
36.
37.
Jiang X, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol. 2018;163–164:144–71.PubMedCrossRef
38.
39.
40.
41.
42.
43.
Abbott NJ, et al. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25.PubMedCrossRef
44.
Castellanos M, et al. Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke: a multicenter confirmatory study. Stroke. 2007;38(6):1855–9.PubMedCrossRef
45.
Castellanos M, et al. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke. 2003;34(1):40–6.PubMedCrossRef
46.
Romanic AM, Madri JA. Extracellular matrix-degrading proteinases in the nervous system. Brain Pathol. 1994;4(2):145–56.PubMedCrossRef
47.
Rosenberg GA, et al. Collagenase-induced intracerebral hemorrhage in rats. Stroke. 1990;21(5):801–7.PubMedCrossRef
48.
Khatri R, et al. Blood-brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke. Neurology. 2012;79(13 Suppl 1):S52–7.PubMedCrossRef
49.
Lin L, Wang X, Yu Z. Ischemia-reperfusion injury in the brain: mechanisms and potential therapeutic strategies. Biochem Pharmacol (Los Angel). 2016;5(4).
50.
Teng D, et al. Endothelial trauma from mechanical thrombectomy in acute stroke: in vitro live-cell platform with animal validation. Stroke. 2015;46(4):1099–106.PubMedCrossRef
51.
Yepes M, et al. Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J Clin Invest. 2003;112(10):1533–40.PubMedPubMedCentralCrossRef
52.
Wang X, et al. Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator. Nat Med. 2003;9(10):1313–7.PubMedCrossRef
53.
Siao CJ, Tsirka SE. Tissue plasminogen activator mediates microglial activation via its finger domain through annexin II. J Neurosci. 2002;22(9):3352–8.PubMedPubMedCentralCrossRef
54.
Su EJ, et al. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke. Nat Med. 2008;14(7):731–7.PubMedPubMedCentralCrossRef
55.
Simão F, et al. Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke. Blood. 2017;129(16):2280–90.PubMedPubMedCentralCrossRef
56.
Shi K, et al. tPA mobilizes immune cells that exacerbate hemorrhagic transformation in stroke. Circ Res. 2021;128(1):62–75.PubMedCrossRef
57.
Jickling GC, et al. Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab. 2014;34(2):185–99.PubMedCrossRef
58.
Whiteley WN, et al. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies. Stroke. 2012;43(11):2904–9.PubMedCrossRef
59.
Kidwell CS, et al. Predictors of hemorrhagic transformation in patients receiving intra-arterial thrombolysis. Stroke. 2002;33(3):717–24.PubMedCrossRef
60.
61.
Desilles JP, et al. Diabetes mellitus, admission glucose, and outcomes after stroke thrombolysis: a registry and systematic review. Stroke. 2013;44(7):1915–23.PubMedCrossRef
62.
Johnston KC, et al. Intensive vs standard treatment of hyperglycemia and functional outcome in patients with acute ischemic stroke: the SHINE randomized clinical trial. JAMA. 2019;322(4):326–35.PubMedPubMedCentralCrossRef
63.
Gray CS, et al. Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol. 2007;6(5):397–406.PubMedCrossRef
64.
65.
Mohammadi MT, Dehghani GA. Acute hypertension induces brain injury and blood-brain barrier disruption through reduction of claudins mRNA expression in rat. Pathol Res Pract. 2014;210(12):985–90.PubMedCrossRef
66.
67.
Mazya M, 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(6):1524–31.PubMedCrossRef
68.
Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Int. 2009;22(11):1041–50.PubMedCrossRef
69.
Yang P, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med. 2020;382(21):1981–93.PubMedCrossRef
70.
71.
Langel C, Popovic KS. Infarct-core CT perfusion parameters in predicting post-thrombolysis hemorrhagic transformation of acute ischemic stroke. Radiol Oncol. 2018;53(1):25–30.PubMedPubMedCentralCrossRef
72.
Lee YB, et al. Predictors and impact of hemorrhagic transformations after endovascular thrombectomy in patients with acute large vessel occlusions. J Neurointerv Surg. 2019;11(5):469–73.PubMedCrossRef
73.
Nogueira RG, et al. Predictors and clinical relevance of hemorrhagic transformation after endovascular therapy for anterior circulation large vessel occlusion strokes: a multicenter retrospective analysis of 1122 patients. J Neurointerv Surg. 2015;7(1):16–21.PubMedCrossRef
74.
Luby M, et al. Frequency of blood-brain barrier disruption post-endovascular therapy and multiple thrombectomy passes in acute ischemic stroke patients. Stroke. 2019;50(8):2241–4.PubMedPubMedCentralCrossRef
75.
Stone JA, et al. Therapies for hemorrhagic transformation in acute ischemic stroke. Curr Treat Options Neurol. 2017;19(1):1.PubMedCrossRef
76.
Chen C, et al. Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial. EClinicalMedicine. 2023;57:101849.PubMedPubMedCentralCrossRef
77.
Samuels N, et al. Admission systolic blood pressure and effect of endovascular treatment in patients with ischaemic stroke: an individual patient data meta-analysis. Lancet Neurol. 2023;22(4):312–9.PubMedCrossRef
78.
Wang J, et al. Spontaneous cerebellar hemorrhage with severe brainstem dysfunction through minimally invasive puncture treatment by locating the simple bedside. Medicine (Baltimore). 2019;98(38):e17211.PubMedCrossRef
79.
Hernández-Durán S, et al. Decompressive craniectomy in malignant stroke after hemorrhagic transformation. Stroke. 2021;52(8):e486–7.PubMedCrossRef
80.
81.
Mistry EA, et al. Systolic blood pressure within 24 hours after thrombectomy for acute ischemic stroke correlates with outcome. J Am Heart Assoc. 2017;6(5).
82.
Goyal N, et al. Blood pressure levels post mechanical thrombectomy and outcomes in large vessel occlusion strokes. Neurology. 2017;89(6):540–7.PubMedCrossRef
83.
Kim TJ, et al. Blood pressure variability and hemorrhagic transformation in patients with successful recanalization after endovascular recanalization therapy: a retrospective observational study. Ann Neurol. 2019;85(4):574–81.PubMedCrossRef
84.
Malhotra K, et al. Association of blood pressure with outcomes in acute stroke thrombectomy. Hypertension. 2020;75(3):730–9.PubMedCrossRef
85.
Powers WJ, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–110.PubMedCrossRef
86.
Anderson CS, et al. Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial. Lancet. 2019;393(10174):877–88.PubMedCrossRef
87.
Yong M, Kaste M. Association of characteristics of blood pressure profiles and stroke outcomes in the ECASS-II trial. Stroke. 2008;39(2):366–72.PubMedCrossRef
88.
Stead LG, et al. Impact of acute blood pressure variability on ischemic stroke outcome. Neurology. 2006;66(12):1878–81.PubMedCrossRef
89.
Petersen NH, et al. Association of personalized blood pressure targets with hemorrhagic transformation and functional outcome after endovascular stroke therapy. JAMA Neurol. 2019;76(10):1256–8.PubMedPubMedCentralCrossRef
90.
Silverman A, et al. Deviation from personalized blood pressure targets is associated with worse outcome after subarachnoid hemorrhage. Stroke. 2019;50(10):2729–37.PubMedPubMedCentralCrossRef
91.
Petersen NH, et al. Fixed compared with autoregulation-oriented blood pressure thresholds after mechanical thrombectomy for ischemic stroke. Stroke. 2020;51(3):914–21.PubMedPubMedCentralCrossRef
92.
Beqiri E, et al. Feasibility of individualised severe traumatic brain injury management using an automated assessment of optimal cerebral perfusion pressure: the COGiTATE phase II study protocol. BMJ Open. 2019;9(9):e030727.PubMedPubMedCentralCrossRef
93.
Donnelly J, et al. Individualizing thresholds of cerebral perfusion pressure using estimated limits of autoregulation. Crit Care Med. 2017;45(9):1464–71.PubMedPubMedCentralCrossRef
94.
Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev. 1990;2(2):161–92.PubMed
95.
Wang A, Ortega-Gutierrez S, Petersen NH. Autoregulation in the neuro ICU. Curr Treat Options Neurol. 2018;20(6):20.PubMedCrossRef
96.
Xiong L, et al. Impaired cerebral autoregulation: measurement and application to stroke. J Neurol Neurosurg Psychiatry. 2017;88(6):520–31.PubMedCrossRef
97.
Fiorelli M, et al. Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort. Stroke. 1999;30(11):2280–4.PubMedCrossRef
98.
Mac Grory B, et al. Anticoagulation resumption after stroke from atrial fibrillation. Curr Atheroscler Rep. 2019;21(8):29.PubMedCrossRef
99.
Külkens S, Hacke W. Thrombolysis with alteplase for acute ischemic stroke: review of SITS-MOST and other Phase IV studies. Expert Rev Neurother. 2007;7(7):783–8.PubMedCrossRef
100.
Chen Z, et al. Contrast extravasation is predictive of poor clinical outcomes in patients undergoing endovascular therapy for acute ischemic stroke in the anterior circulation. J Stroke Cerebrovasc Dis. 2020;29(1):104494.PubMedCrossRef
101.
Phan CM, et al. Differentiation of hemorrhage from iodinated contrast in different intracranial compartments using dual-energy head CT. AJNR Am J Neuroradiol. 2012;33(6):1088–94.PubMedPubMedCentralCrossRef
102.
Beslow LA, et al. Association of pediatric ASPECTS and NIH stroke scale, hemorrhagic transformation, and 12-month outcome in children with acute ischemic stroke. Neurology. 2021.
103.
Powers WJ, et al. 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: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344–418.PubMedCrossRef
104.
Donahue J, Wintermark M. Perfusion CT and acute stroke imaging: foundations, applications, and literature review. J Neuroradiol. 2015;42(1):21–9.PubMedCrossRef
105.
Heye AK, et al. Assessment of blood-brain barrier disruption using dynamic contrast-enhanced MRI. A systematic review. Neuroimage Clin. 2014;6:262–74.PubMedPubMedCentralCrossRef
106.
Mallick AA, et al. Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol. 2014;13(1):35–43.PubMedCrossRef
107.
Fullerton HJ, et al. Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging. Pediatrics. 2007;119(3):495–501.PubMedCrossRef
108.
Fullerton HJ, et al. Risk of stroke in children: ethnic and gender disparities. Neurology. 2003;61(2):189–94.PubMedCrossRef
109.
Grunt S, et al. Cerebral sinus venous thrombosis in Swiss children. Dev Med Child Neurol. 2010;52(12):1145–50.PubMedCrossRef
110.
111.
Hutchinson ML, Beslow LA. Hemorrhagic transformation of arterial ischemic and venous stroke in children. Pediatr Neurol. 2019;95:26–33.PubMedCrossRef
112.
113.
Bigi S, et al. Feasibility, safety, and outcome of recanalization treatment in childhood stroke. Ann Neurol. 2018;83(6):1125–32.PubMedCrossRef
Metadata
Title
Hemorrhagic Conversion of Acute Ischemic Stroke
Authors
Adeel S. Zubair
Kevin N. Sheth
Publication date
01-04-2023
Publisher
Springer International Publishing
Published in
Neurotherapeutics / Issue 3/2023
Print ISSN: 1933-7213
Electronic ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-023-01377-1

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