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Early embolic events complicating intravenous thrombolysis for acute ischemic stroke
American Journal of Emergency Medicine (2012) 30, 2079.e3–2079.e5
www.elsevier.com/locate/ajem
Case Report Early embolic events complicating intravenous thrombolysis for acute ischemic stroke Abstract Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy. It suggested a central embolic source. Because the patient has paroxysmal atrial fibrillation (Af), the possible embolic sources may come from fragmentation of pre-existing intra-atrial clot. Although Af and the presence of cardiac thrombus are not contraindication for IV rt-PA in acute ischemic stroke, our case and review suggested that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke and has been widely administered in the 3-hour window. However, patients may experience early neurologic deterioration after treatment with IV rt-PA. Mechanisms of early neurologic deterioration after treatment with IV rt-PA include symptomatic intracerebral hemorrhage (ICH), arterial reocclusion, and early recurrent ischemic stroke involving an initially unaffected arterial territory. We reported a rare case of acute ischemic stroke that developed acute deterioration after treatment with IV rt-PA due to recurrent ischemic stroke in different arterial territory and systemic embolic events. A 72-year-old man, with a medical history of hypertension and ischemic heart disease, was admitted to the emergency department because of sudden onset of consciousness change and right hemiparesis. On examination, his blood pressure was 172/89 mm Hg, and Glasgow Coma Scale was E4V1M5. Electrocardiography showed sinus rhythm. The initial National Institute of Health Stroke Scale was 21. The platelet count and coagulation times were 0735-6757/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
both within normal limits. Brain computed tomographic (CT) scan showed no evidence of hemorrhage and no hypodensity lesion. Intravenous recombinant tissue plasminogen activator was prescribed under the diagnosis of acute ischemic stroke. Neurologic symptoms improved to National Institute of Health Stroke Scale 9 after thrombolysis 24 hours, and a follow-up brain CT showed hypodensity lesion in the territory of left anterior cerebral artery (ACA) (Fig. 1A). Paroxysmal atrial fibrillation (Af) was noted after admission. Deterioration of right hemiparesis occurred on the fourth day after thrombolysis, and a repeated brain CT showed no ICH and no change of hypodensity lesion in the territory of left ACA (Fig. 1B). Arterial reocclusion was favored, and low-molecular-weight heparin therapy was administered. Furthermore, left side limbs weakness and bilateral eyeballs conjugate deviated to the right side with deep coma occurred on the fifth days. Brain CT disclosed no change of hypodensity lesion in the territory of left ACA but interval development of minimal subarachnoid hemorrhage in left frontal area (Fig. 1C). The patient was intubated for respiratory failure. Early recurrent ischemic stroke in right middle cerebral artery (MCA) territory was favored. Low-molecular-weight heparin therapy was discontinued because of minimal subarachnoid hemorrhage. Acute cyanosis of right lower limb without distal pulses happened, and clinical suspicion of peripheral arterial embolism was favored. Transesophageal echocardiography and angiography were not performed because of the lack of therapeutic consequences and critical medical condition. The patient died of multiple organ failure finally. Systemic embolization and, in particular, embolic stroke have been observed in patients receiving systemic thrombolysis for acute myocardial infarction and prosthetic valve thrombosis. Fragmentation of a pre-existing intracardiac thrombus was suggested as the most probable underlying mechanism [1]. However, very few reports are available to evaluate the risk of thrombolysis in stroke patients with cardiac thrombus. One study reported 5 patients with cardiac thrombus who received IV rt-PA for stroke. Their data suggest that the presence of a cardiac thrombus is not associated with a high risk of recurrent embolism in patients with stroke who are given IV rt-PA [2]. Other studies reported embolic events after thrombolysis in stroke. Kissela et al [3] presented a case of early recurrent ischemic stroke due to calcific embolization after IV rt-PA therapy for acute
2079.e4
Case Report
Fig. 1 A, Brain CT disclosed hypodensity lesion in the territory of left ACA 24 hours after IV rt-PA thrombolysis. B, Brain CT disclosed no ICH and no change of hypodensity lesion in the territory of left ACA on the fourth day after IV rt-PA thrombolysis. C, Brain CT disclosed no change of hypodensity lesion in the territory of left ACA but interval development of minimal subarachnoid hemorrhage in left frontal area.
ischemic stroke. Garg et al [4] presented a case of early recurrent ischemic stroke due to dislodgement of cardiac thrombus by IV rt-PA thrombolytic therapy. Georgiadis et al [5] presented multifocal embolic vessel occlusions, including cerebral and renal arteries, in another 2 patients after IV rt-PA therapy for acute ischemic stroke. Lai and Hu [6] and Yalcin-Cakmakli et al [7] presented another 2 cases of early recurrent ischemic stroke after IV rt-PA therapy for acute ischemic stroke, and both have Af. Awadh et al [8] concluded that the incidence of early recurrent ischemic stroke after IV rt-PA was 2.6% and was associated with previous Af. Besides early recurrent stroke, possible embolization to other vascular beds has also been documented after IV rt-PA for ischemic stroke, including acute myocardial infarction [9,10], peripheral arterial embolism [11], and embolism to the external carotid artery [12]. Because of echocardiographic screening of every patient would delay thrombolysis and considering the definite benefit associated with earlier thrombolytic treatment, there is no guideline-recommended echocardiography to exclude intracardiac thrombus before IV rt-PA for stroke. The presence of Af on admission electrocardiograph alone is insensitive. Although Af and the presence of cardiac thrombus are not contraindicated for IV rt-PA in acute ischemic stroke, our case and review suggest that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. Because of the increased risk of ICH in cardioembolic stroke, the safety and effect of administration of anticoagulants or additional dose of recombinant tissue plasminogen activator therapy for early recurrent ischemic stroke in these patients are not clear. Interventional treatment, including intra-arterial or mechanical thrombolysis, may be taken into
consideration. Further study and experience are needed to clarify these problems.
Ping Song Chou MD Department of Neurology Kaohsiung Medical University Hospital Kaohsiung 807, Taiwan Chien Hung Lin MD Department of Diagnostic Radiology Chi-Mei Medical Center Yung Kang City, Tainan 710, Taiwan Hai Lun Chao PhD Department of Health Care Administration Chung-Hwa University of Medical Technology Tainan 717, Taiwan A Ching Chao MD Department of Neurology Kaohsiung Medical University Hospital Kaohsiung 807, Taiwan Department of and Master's Program in Neurology Faculty of Medicine College of Medicine Kaohsiung Medical University Kaohsiung 807, Taiwan Department of Neurology Kaohsiung Municipal Ta-Tung Hospital Kaohsiung, Taiwan E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2011.10.016
Case Report
References [1] Stafford PJ, Strachan CJ, Vincent R, et al. Multiple microemboli after disintegration of clot during thrombolysis for acute myocardial infarction. BMJ 1989;299(6711):1310-2. [2] Derex L, Nighoghossian N, Perinetti M, et al. Thrombolytic therapy in acute ischemic stroke patients with cardiac thrombus. Neurology 2001;57(11):2122-5. [3] Kissela BM, Kothari RU, Tomsick TA, et al. Embolization of calcific thrombi after tissue plasminogen activator treatment. J Stroke Cerebrovasc Dis 2001;10:135-8. [4] Garg A, Yaduvanshi A, Mohindra KD. Cardioembolic stroke on unaffected side during thrombolysis for acute ischemic stroke. Neurol India 2010;58(1):112-4. [5] Georgiadis D, Engelter S, Tettenborn B, et al. Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis. Circulation 2006;114:237-41. [6] Lai CC, Hu CJ. A left MCA territory infarction during intravenous recombinant tissue plasminogen activator therapy for right MCA territory ischaemic stroke. Emerg Med J 2006;23:e11.
2079.e5 [7] Yalcin-Cakmakli G, Akpinar E, Topcuoglu MA, et al. Right internal carotid artery occlusion during intravenous thrombolysis for left middle cerebral artery occlusion. J Stroke Cerebrovasc Dis 2009;18: 74-7. [8] Awadh M, MacDougall N, Santosh C, et al. Early recurrent ischemic stroke complicating intravenous thrombolysis for stroke: incidence and association with atrial fibrillation. Stroke 2010;41(9): 1990-5. [9] Meissner W, Lempert T, Saeuberlich-Kniggeb S, et al. Fatal embolic myocardial infarction after systemic thrombolysis for stroke. Cerebrovasc Dis 2006;22:213-4. [10] Mehdiratta M, Murphy C, Al-Harthi A, et al. Myocardial infarction following t-PA for acute stroke. Can J Neurol Sci 2007;34: 417-20. [11] Gomez-Beldarrain M, Telleria M, Garcia-Monco JC. Peripheral arterial embolism during thrombolysis for stroke. Neurology 2006; 67:1096-7. [12] Yasaka M, Yamaguchi T, Yonehara T, et al. Recurrent embolization during intravenous administration of tissue plasminogen activator in acute cardioembolic stroke: a case report. Angiology 1994; 45:481-4.
www.elsevier.com/locate/ajem
Case Report Early embolic events complicating intravenous thrombolysis for acute ischemic stroke Abstract Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy. It suggested a central embolic source. Because the patient has paroxysmal atrial fibrillation (Af), the possible embolic sources may come from fragmentation of pre-existing intra-atrial clot. Although Af and the presence of cardiac thrombus are not contraindication for IV rt-PA in acute ischemic stroke, our case and review suggested that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke and has been widely administered in the 3-hour window. However, patients may experience early neurologic deterioration after treatment with IV rt-PA. Mechanisms of early neurologic deterioration after treatment with IV rt-PA include symptomatic intracerebral hemorrhage (ICH), arterial reocclusion, and early recurrent ischemic stroke involving an initially unaffected arterial territory. We reported a rare case of acute ischemic stroke that developed acute deterioration after treatment with IV rt-PA due to recurrent ischemic stroke in different arterial territory and systemic embolic events. A 72-year-old man, with a medical history of hypertension and ischemic heart disease, was admitted to the emergency department because of sudden onset of consciousness change and right hemiparesis. On examination, his blood pressure was 172/89 mm Hg, and Glasgow Coma Scale was E4V1M5. Electrocardiography showed sinus rhythm. The initial National Institute of Health Stroke Scale was 21. The platelet count and coagulation times were 0735-6757/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
both within normal limits. Brain computed tomographic (CT) scan showed no evidence of hemorrhage and no hypodensity lesion. Intravenous recombinant tissue plasminogen activator was prescribed under the diagnosis of acute ischemic stroke. Neurologic symptoms improved to National Institute of Health Stroke Scale 9 after thrombolysis 24 hours, and a follow-up brain CT showed hypodensity lesion in the territory of left anterior cerebral artery (ACA) (Fig. 1A). Paroxysmal atrial fibrillation (Af) was noted after admission. Deterioration of right hemiparesis occurred on the fourth day after thrombolysis, and a repeated brain CT showed no ICH and no change of hypodensity lesion in the territory of left ACA (Fig. 1B). Arterial reocclusion was favored, and low-molecular-weight heparin therapy was administered. Furthermore, left side limbs weakness and bilateral eyeballs conjugate deviated to the right side with deep coma occurred on the fifth days. Brain CT disclosed no change of hypodensity lesion in the territory of left ACA but interval development of minimal subarachnoid hemorrhage in left frontal area (Fig. 1C). The patient was intubated for respiratory failure. Early recurrent ischemic stroke in right middle cerebral artery (MCA) territory was favored. Low-molecular-weight heparin therapy was discontinued because of minimal subarachnoid hemorrhage. Acute cyanosis of right lower limb without distal pulses happened, and clinical suspicion of peripheral arterial embolism was favored. Transesophageal echocardiography and angiography were not performed because of the lack of therapeutic consequences and critical medical condition. The patient died of multiple organ failure finally. Systemic embolization and, in particular, embolic stroke have been observed in patients receiving systemic thrombolysis for acute myocardial infarction and prosthetic valve thrombosis. Fragmentation of a pre-existing intracardiac thrombus was suggested as the most probable underlying mechanism [1]. However, very few reports are available to evaluate the risk of thrombolysis in stroke patients with cardiac thrombus. One study reported 5 patients with cardiac thrombus who received IV rt-PA for stroke. Their data suggest that the presence of a cardiac thrombus is not associated with a high risk of recurrent embolism in patients with stroke who are given IV rt-PA [2]. Other studies reported embolic events after thrombolysis in stroke. Kissela et al [3] presented a case of early recurrent ischemic stroke due to calcific embolization after IV rt-PA therapy for acute
2079.e4
Case Report
Fig. 1 A, Brain CT disclosed hypodensity lesion in the territory of left ACA 24 hours after IV rt-PA thrombolysis. B, Brain CT disclosed no ICH and no change of hypodensity lesion in the territory of left ACA on the fourth day after IV rt-PA thrombolysis. C, Brain CT disclosed no change of hypodensity lesion in the territory of left ACA but interval development of minimal subarachnoid hemorrhage in left frontal area.
ischemic stroke. Garg et al [4] presented a case of early recurrent ischemic stroke due to dislodgement of cardiac thrombus by IV rt-PA thrombolytic therapy. Georgiadis et al [5] presented multifocal embolic vessel occlusions, including cerebral and renal arteries, in another 2 patients after IV rt-PA therapy for acute ischemic stroke. Lai and Hu [6] and Yalcin-Cakmakli et al [7] presented another 2 cases of early recurrent ischemic stroke after IV rt-PA therapy for acute ischemic stroke, and both have Af. Awadh et al [8] concluded that the incidence of early recurrent ischemic stroke after IV rt-PA was 2.6% and was associated with previous Af. Besides early recurrent stroke, possible embolization to other vascular beds has also been documented after IV rt-PA for ischemic stroke, including acute myocardial infarction [9,10], peripheral arterial embolism [11], and embolism to the external carotid artery [12]. Because of echocardiographic screening of every patient would delay thrombolysis and considering the definite benefit associated with earlier thrombolytic treatment, there is no guideline-recommended echocardiography to exclude intracardiac thrombus before IV rt-PA for stroke. The presence of Af on admission electrocardiograph alone is insensitive. Although Af and the presence of cardiac thrombus are not contraindicated for IV rt-PA in acute ischemic stroke, our case and review suggest that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. Because of the increased risk of ICH in cardioembolic stroke, the safety and effect of administration of anticoagulants or additional dose of recombinant tissue plasminogen activator therapy for early recurrent ischemic stroke in these patients are not clear. Interventional treatment, including intra-arterial or mechanical thrombolysis, may be taken into
consideration. Further study and experience are needed to clarify these problems.
Ping Song Chou MD Department of Neurology Kaohsiung Medical University Hospital Kaohsiung 807, Taiwan Chien Hung Lin MD Department of Diagnostic Radiology Chi-Mei Medical Center Yung Kang City, Tainan 710, Taiwan Hai Lun Chao PhD Department of Health Care Administration Chung-Hwa University of Medical Technology Tainan 717, Taiwan A Ching Chao MD Department of Neurology Kaohsiung Medical University Hospital Kaohsiung 807, Taiwan Department of and Master's Program in Neurology Faculty of Medicine College of Medicine Kaohsiung Medical University Kaohsiung 807, Taiwan Department of Neurology Kaohsiung Municipal Ta-Tung Hospital Kaohsiung, Taiwan E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2011.10.016
Case Report
References [1] Stafford PJ, Strachan CJ, Vincent R, et al. Multiple microemboli after disintegration of clot during thrombolysis for acute myocardial infarction. BMJ 1989;299(6711):1310-2. [2] Derex L, Nighoghossian N, Perinetti M, et al. Thrombolytic therapy in acute ischemic stroke patients with cardiac thrombus. Neurology 2001;57(11):2122-5. [3] Kissela BM, Kothari RU, Tomsick TA, et al. Embolization of calcific thrombi after tissue plasminogen activator treatment. J Stroke Cerebrovasc Dis 2001;10:135-8. [4] Garg A, Yaduvanshi A, Mohindra KD. Cardioembolic stroke on unaffected side during thrombolysis for acute ischemic stroke. Neurol India 2010;58(1):112-4. [5] Georgiadis D, Engelter S, Tettenborn B, et al. Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis. Circulation 2006;114:237-41. [6] Lai CC, Hu CJ. A left MCA territory infarction during intravenous recombinant tissue plasminogen activator therapy for right MCA territory ischaemic stroke. Emerg Med J 2006;23:e11.
2079.e5 [7] Yalcin-Cakmakli G, Akpinar E, Topcuoglu MA, et al. Right internal carotid artery occlusion during intravenous thrombolysis for left middle cerebral artery occlusion. J Stroke Cerebrovasc Dis 2009;18: 74-7. [8] Awadh M, MacDougall N, Santosh C, et al. Early recurrent ischemic stroke complicating intravenous thrombolysis for stroke: incidence and association with atrial fibrillation. Stroke 2010;41(9): 1990-5. [9] Meissner W, Lempert T, Saeuberlich-Kniggeb S, et al. Fatal embolic myocardial infarction after systemic thrombolysis for stroke. Cerebrovasc Dis 2006;22:213-4. [10] Mehdiratta M, Murphy C, Al-Harthi A, et al. Myocardial infarction following t-PA for acute stroke. Can J Neurol Sci 2007;34: 417-20. [11] Gomez-Beldarrain M, Telleria M, Garcia-Monco JC. Peripheral arterial embolism during thrombolysis for stroke. Neurology 2006; 67:1096-7. [12] Yasaka M, Yamaguchi T, Yonehara T, et al. Recurrent embolization during intravenous administration of tissue plasminogen activator in acute cardioembolic stroke: a case report. Angiology 1994; 45:481-4.