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Serendipitous Recanalization of Basilar Artery Occlusion
Case Report
Serendipitous Recanalization of Basilar Artery Occlusion Jeffrey A. Switzer, DO, MCTS,* Scott E. Forseen, MD,† Askiel Bruno, MD,* and David C. Hess, MD*
Objective: To describe a case of recanalization of a basilar artery occlusion with intravenous (IV) tenecteplase. Case: A 74-year-old man with a history of cardiomyopathy presented to an outside hospital with acute vertigo, dysarthria, gaze deviation, and ataxia. Computerized tomography arteriography demonstrated occlusion of the proximal basilar artery. IV tissue plasminogen activator was ordered; however, the patient received a cardiac dose of IV tenecteplase. The patient was transferred to our facility, whereby symptoms resolved, and repeat computerized tomography arteriography displayed recanalization of the basilar artery. Conclusions: Tenecteplase has enhanced biochemical and pharmacokinetic properties that may be ideal for treatment of basilar artery occlusion and should be further investigated in a randomized clinical trial. Key Words: Basilar artery occlusion—thrombolytic therapy—acute stroke—tenecteplase. Ó 2013 by National Stroke Association
Outcome from basilar artery occlusion (BAO) is often poor and the optimal strategy to achieve reperfusion is uncertain.1-3 Intravenous (IV) tissue plasminogen activator (tPA) may be ineffective, particularly in proximal-tomid-BAO,4 and endovascular revascularization strategies are frequently attempted.5 Tenecteplase is a genetically modified tPA with longer half-life, increased fibrin specificity, and plasminogen activator inhibitor-1 resistance.6 Compared with tPA, tenecteplase may increase recanalization and improve outcome in selected middle cerebral artery territory occlusions.7 A
From the *Department of Neurology, Georgia Regents University, Augusta, GA; and †Department of Radiology, Georgia Regents University, Augusta, GA. Received March 1, 2013; revision received May 17, 2013; accepted June 8, 2013. Disclosures: None. Sources of funding: None. Address correspondence to Jeffrey A. Switzer, DO, MCTS, Department of Neurology, 1122, 15th St, Augusta, GA 30912. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2013 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.06.019
phase IIB trial of tenecteplase in unselected patients was terminated prematurely because of slow enrollment,8 and tPA remains the only approved fibrinolytic for acute stroke. We present a patient with BAO who mistakenly received IV tenecteplase with recanalization and resolution of neurologic deficits.
Case Report A 74-year-old man with a history of dilated cardiomyopathy developed sudden onset of vertigo, nausea, vomiting, and dysarthria. He was taken to a local emergency department where his symptoms progressed to include bilateral hearing loss. Examination revealed left gaze paresis and dysmetria on finger-to-nose and heel–knee–shin bilaterally. Computed tomography angiography showed proximal thrombosis of the BA (Fig 1). IV tPA was ordered 5 hours after symptom onset; however, as a result of an apparent pharmacy error, a high dose of tenecteplase (50 mg, .53 mg/kg) was administered. The patient was transferred to our hospital for consideration of endovascular revascularization. The error in drug delivery was not noted until arrival at our hospital and after the infusion was complete.
Journal of Stroke and Cerebrovascular Diseases, Vol. 22, No. 8 (November), 2013: pp e671-e673
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J.A. SWITZER ET AL.
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Figure 1. Three-dimensional reconstruction of computed tomography arteriogram displaying lack of blood flow in distal vertebral arteries and proximal basilar artery (A) and complete recanalization post-tenecteplase (B).
On arrival, the patient was significantly improved and neurologic examination revealed only mild dysarthria that resolved over several hours. A repeat computed tomography angiography demonstrated complete recanalization (TIMI 3) of the BA without brain infarction or hemorrhage (Fig 1).
Discussion We describe the first case of IV tenecteplase for BAO that we are aware of with resulting recanalization and favorable outcome. Although functional outcome from BAO is quite variable, IV tPA is often ineffective for proximal or large clot burdens.4 Although bridging strategies, intra-arterial fibrinolysis, or mechanical thrombectomy may potentially be more effective, none have been tested in randomized clinical trials of BAO. Furthermore, these strategies are restricted to tertiary centers with endovascular capabilities. Fibrinolytic agents that could be administered IV and achieve rapid recanalization more effectively than IV tPA are, therefore, appealing. Tenecteplase was engineered to enhance the safety and efficacy of tPA. In a dose-escalation trial of IV tenecteplase for acute myocardial infarction, doses of 30-50 mg achieved complete reperfusion in 57%-64% of patients.9 Whether IV tenecteplase improves clinical outcome compared with IV tPA in stroke is undetermined8; however, patients with large artery occlusion involving the MCA and an associated perfusion mismatch had higher recanalization rates and better functional outcomes compared with IV tPA.7 A dose-escalation trial of IV tenecteplase in acute stroke demonstrated an increase rate of symptomatic intracranial hemorrhage at doses of .5 mg/kg.10 However, the
risk of symptomatic intracranial hemorrhage may be lower in patients with posterior circulation strokes11,12 potentially permitting the safe administration of higher fibrinolytic doses. Our patient received a standard cardiac dose of 50 mg (.53 mg/kg). Considering the potentially grave prognosis of persistent BAO, such a dose of tenecteplase may be warranted. Higher doses of tenecteplase may be needed in patients with a greater clot burden to achieve recanalization. Randomized clinical trials of IV tenecteplase, desmoteplase, or other newer generation fibrinolytics in BAO should be considered.
References 1. Schonewille WJ, Wijman CA, Michel P, et al. Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study. Lancet Neurol 2009; 8:724-730. 2. Brandt T, von Kummer R, M€ uller-K€ uppers M, et al. Thrombolytic therapy of acute basilar artery occlusion. Stroke 1996;27:875-881. 3. Hacke W, Zeumer H, Ferbert A, et al. Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. Stroke 1988; 19:1216-1222. 4. Sairanen T, Strbian D, Soinne L, , et alGroup ftHSTR. Intravenous thrombolysis of basilar artery occlusion. Stroke 2011;42:2175-2179. 5. Ottomeyer C, Zeller J, Fesl G, et al. Multimodal recanalization therapy in acute basilar artery occlusion. Stroke 2012;43:2130-2135. 6. Lyden P. Tenecteplase for acute ischemic stroke. Int J Stroke 2011;6:509-510. 7. Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 2012;366:1099-1107.
SERENDIPITOUS RECANALIZATION OF BASILAR ARTERY OCCLUSION 8. Haley EC, Jr, Thompson JLP, Grotta JC, et al. Tenecteplase in Stroke I. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke 2010;41:707-711. 9. Cannon CP, McCabe CH, Gibson CM, et al. TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation 1997; 95:351-356.
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10. Haley EC, Jr, Lyden PD, Johnston KC, et al, Investigators TNKiS. A pilot dose-escalationsafety study of tenecteplase in acute ischemic stroke. Stroke 2005;36:607-612. 11. Sarikaya H, Arnold M, Engelter ST, et al. Outcomes of intravenous thrombolysis in posterior versus anterior circulation stroke. Stroke 2011;42:2498-2502. 12. Lee M, Saver JL, Alger JR, et al. Blood-brain barrier permeability derangements in posterior circulation ischemic stroke: frequency and relation to hemorrhagic transformation. J Neurol Sci 2012;313:142-146.
Serendipitous Recanalization of Basilar Artery Occlusion Jeffrey A. Switzer, DO, MCTS,* Scott E. Forseen, MD,† Askiel Bruno, MD,* and David C. Hess, MD*
Objective: To describe a case of recanalization of a basilar artery occlusion with intravenous (IV) tenecteplase. Case: A 74-year-old man with a history of cardiomyopathy presented to an outside hospital with acute vertigo, dysarthria, gaze deviation, and ataxia. Computerized tomography arteriography demonstrated occlusion of the proximal basilar artery. IV tissue plasminogen activator was ordered; however, the patient received a cardiac dose of IV tenecteplase. The patient was transferred to our facility, whereby symptoms resolved, and repeat computerized tomography arteriography displayed recanalization of the basilar artery. Conclusions: Tenecteplase has enhanced biochemical and pharmacokinetic properties that may be ideal for treatment of basilar artery occlusion and should be further investigated in a randomized clinical trial. Key Words: Basilar artery occlusion—thrombolytic therapy—acute stroke—tenecteplase. Ó 2013 by National Stroke Association
Outcome from basilar artery occlusion (BAO) is often poor and the optimal strategy to achieve reperfusion is uncertain.1-3 Intravenous (IV) tissue plasminogen activator (tPA) may be ineffective, particularly in proximal-tomid-BAO,4 and endovascular revascularization strategies are frequently attempted.5 Tenecteplase is a genetically modified tPA with longer half-life, increased fibrin specificity, and plasminogen activator inhibitor-1 resistance.6 Compared with tPA, tenecteplase may increase recanalization and improve outcome in selected middle cerebral artery territory occlusions.7 A
From the *Department of Neurology, Georgia Regents University, Augusta, GA; and †Department of Radiology, Georgia Regents University, Augusta, GA. Received March 1, 2013; revision received May 17, 2013; accepted June 8, 2013. Disclosures: None. Sources of funding: None. Address correspondence to Jeffrey A. Switzer, DO, MCTS, Department of Neurology, 1122, 15th St, Augusta, GA 30912. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2013 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.06.019
phase IIB trial of tenecteplase in unselected patients was terminated prematurely because of slow enrollment,8 and tPA remains the only approved fibrinolytic for acute stroke. We present a patient with BAO who mistakenly received IV tenecteplase with recanalization and resolution of neurologic deficits.
Case Report A 74-year-old man with a history of dilated cardiomyopathy developed sudden onset of vertigo, nausea, vomiting, and dysarthria. He was taken to a local emergency department where his symptoms progressed to include bilateral hearing loss. Examination revealed left gaze paresis and dysmetria on finger-to-nose and heel–knee–shin bilaterally. Computed tomography angiography showed proximal thrombosis of the BA (Fig 1). IV tPA was ordered 5 hours after symptom onset; however, as a result of an apparent pharmacy error, a high dose of tenecteplase (50 mg, .53 mg/kg) was administered. The patient was transferred to our hospital for consideration of endovascular revascularization. The error in drug delivery was not noted until arrival at our hospital and after the infusion was complete.
Journal of Stroke and Cerebrovascular Diseases, Vol. 22, No. 8 (November), 2013: pp e671-e673
e671
J.A. SWITZER ET AL.
e672
Figure 1. Three-dimensional reconstruction of computed tomography arteriogram displaying lack of blood flow in distal vertebral arteries and proximal basilar artery (A) and complete recanalization post-tenecteplase (B).
On arrival, the patient was significantly improved and neurologic examination revealed only mild dysarthria that resolved over several hours. A repeat computed tomography angiography demonstrated complete recanalization (TIMI 3) of the BA without brain infarction or hemorrhage (Fig 1).
Discussion We describe the first case of IV tenecteplase for BAO that we are aware of with resulting recanalization and favorable outcome. Although functional outcome from BAO is quite variable, IV tPA is often ineffective for proximal or large clot burdens.4 Although bridging strategies, intra-arterial fibrinolysis, or mechanical thrombectomy may potentially be more effective, none have been tested in randomized clinical trials of BAO. Furthermore, these strategies are restricted to tertiary centers with endovascular capabilities. Fibrinolytic agents that could be administered IV and achieve rapid recanalization more effectively than IV tPA are, therefore, appealing. Tenecteplase was engineered to enhance the safety and efficacy of tPA. In a dose-escalation trial of IV tenecteplase for acute myocardial infarction, doses of 30-50 mg achieved complete reperfusion in 57%-64% of patients.9 Whether IV tenecteplase improves clinical outcome compared with IV tPA in stroke is undetermined8; however, patients with large artery occlusion involving the MCA and an associated perfusion mismatch had higher recanalization rates and better functional outcomes compared with IV tPA.7 A dose-escalation trial of IV tenecteplase in acute stroke demonstrated an increase rate of symptomatic intracranial hemorrhage at doses of .5 mg/kg.10 However, the
risk of symptomatic intracranial hemorrhage may be lower in patients with posterior circulation strokes11,12 potentially permitting the safe administration of higher fibrinolytic doses. Our patient received a standard cardiac dose of 50 mg (.53 mg/kg). Considering the potentially grave prognosis of persistent BAO, such a dose of tenecteplase may be warranted. Higher doses of tenecteplase may be needed in patients with a greater clot burden to achieve recanalization. Randomized clinical trials of IV tenecteplase, desmoteplase, or other newer generation fibrinolytics in BAO should be considered.
References 1. Schonewille WJ, Wijman CA, Michel P, et al. Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study. Lancet Neurol 2009; 8:724-730. 2. Brandt T, von Kummer R, M€ uller-K€ uppers M, et al. Thrombolytic therapy of acute basilar artery occlusion. Stroke 1996;27:875-881. 3. Hacke W, Zeumer H, Ferbert A, et al. Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. Stroke 1988; 19:1216-1222. 4. Sairanen T, Strbian D, Soinne L, , et alGroup ftHSTR. Intravenous thrombolysis of basilar artery occlusion. Stroke 2011;42:2175-2179. 5. Ottomeyer C, Zeller J, Fesl G, et al. Multimodal recanalization therapy in acute basilar artery occlusion. Stroke 2012;43:2130-2135. 6. Lyden P. Tenecteplase for acute ischemic stroke. Int J Stroke 2011;6:509-510. 7. Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 2012;366:1099-1107.
SERENDIPITOUS RECANALIZATION OF BASILAR ARTERY OCCLUSION 8. Haley EC, Jr, Thompson JLP, Grotta JC, et al. Tenecteplase in Stroke I. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke 2010;41:707-711. 9. Cannon CP, McCabe CH, Gibson CM, et al. TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation 1997; 95:351-356.
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10. Haley EC, Jr, Lyden PD, Johnston KC, et al, Investigators TNKiS. A pilot dose-escalationsafety study of tenecteplase in acute ischemic stroke. Stroke 2005;36:607-612. 11. Sarikaya H, Arnold M, Engelter ST, et al. Outcomes of intravenous thrombolysis in posterior versus anterior circulation stroke. Stroke 2011;42:2498-2502. 12. Lee M, Saver JL, Alger JR, et al. Blood-brain barrier permeability derangements in posterior circulation ischemic stroke: frequency and relation to hemorrhagic transformation. J Neurol Sci 2012;313:142-146.