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Safe and Effective Intravenous Thrombolysis for Acute Ischemic Stroke Caused by Left Atrial Myxoma
Case Report
Safe and Effective Intravenous Thrombolysis for Acute Ischemic Stroke Caused by Left Atrial Myxoma Christian D. Nagy, MD,* Michael Levy, MD, PhD,† Thomas J. Mulhearn, IV, MD,‡ Maryam Shapland, MD,x Henry Sun, MD,* David D. Yuh, MD,// Dickson Cheung, MD,x and Nisha Chandra-Strobos, MD*
Atrial myxoma may be associated with syncope or sudden death attributed to leftsided cardiac outflow obstruction or embolization caused by tumor dislodgement or thrombus formation. Definitive treatment for primary and secondary stroke prevention is surgical resection. The role of thrombolysis in acute brain ischemia in patients with atrial myxoma is not defined. There are few data available regarding safety and efficacy of thrombolytic therapy in acute ischemic strokes caused by atrial myxoma. Prior case reports described partial success using intra-arterial local thrombolysis; however, this is invasive and can be associated with significant complications. A previously reported case of systemic thrombolysis resulted in development of cerebral hemorrhage. We describe a young man who presented with syncope and a dense stroke developing as a complication of atrial myxoma, followed by a remarkable recovery after treatment with intravenous recombinant tissue plasminogen activator and urgent cardiac surgery. Contrary to some expert opinion, systemic thrombolytic therapy may be safely and effectively used to treat acute ischemic strokes from atrial myxoma. Key Words: Stroke—atrial myxoma—thrombolysis— recombinant tissue plasminogen activator. Ó 2009 by National Stroke Association
Atrial myxoma is the most common primary heart tumor1 and presents an important diagnostic challenge.2,3 Cerebral infarction is a frequent complication of atrial
From the *Division of Cardiology, †Department of Neurology, xDepartment of Emergency Medicine, //Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland; and ‡Division of Cardiovascular Medicine, Duke University Medical Center, Durham, North Carolina. Received December 19, 2007; revision received November 16, 2008; accepted November 20, 2008. Address correspondence to Nisha Chandra-Strobos, MD, Johns Hopkins Bayview Medical Center, Department of Medicine, Division of Cardiology, 4940 Eastern Ave, Baltimore, MD 21224. E-mail: [email protected]. 1052-3057/$—see front matter Ó 2009 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2008.11.012
398
myxoma and, in addition to dyspnea and palpitation, the most common presentation leading to tumor detection. If the culprit is not identified and promptly removed, recurrent cerebral emboli before cardiac surgery can occur. Emboli from atrial myxoma are composed of thrombus, neoplasm, or a compound of both.4,5 The diagnosis is rarely known at stroke onset and the role of thrombolysis in brain ischemia in patients with atrial myxoma is unknown. We describe a young man who presented with syncope and a dense stroke developing as a complication of atrial myxoma, followed by a remarkable recovery after treatment with intravenous recombinant tissue plasminogen activator (rt-PA) and urgent surgery.
Case Report A previously healthy 26-year-old man was transported to the emergency department after sudden collapse
Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 5 (September-October), 2009: pp 398-402
INTRAVENOUS THROMBOLYSIS IN STROKE AS A RESULT OF MYXOMA
during a game of casual football. He had developed lightheadedness and subsequently fell to the ground. There was no trauma, loss of consciousness, chest pain, shortness of breath, palpitations, vertigo, or preceding aura. There was no seizurelike activity observed. On ambulance arrival he was found to have left-sided hemiparesis. Initial heart rate was 116/min and regular, blood pressure was 163/102 mm Hg, blood sugar was within normal limits, and Glasgow Coma Scale score was 15. On emergency department arrival no jugular venous distention was noted. Heart sounds were normal with an audible S4 and no murmurs, gallop, or rub. Chest and abdominal examination revealed normal findings. Extremities were well perfused. No skin lesions, bruises, or petechiae were identified. Neurologic examination revealed an alert and oriented man with mild dysarthria. Cranial nerve assessment showed left facial weakness presumably caused by upper motor neuron injury; strength was 0/5 in the left upper extremity and 3/5 in the left lower extremity; sensation was lost in the left arm and partially lost in the left leg; coordination was intact. The National Institutes of Health Stroke Scale score was 10. Laboratory work produced normal findings. Electrocardiogram demonstrated sinus tachycardia without left ventricular hypertrophy. Emergency head computed tomography scan without contrast showed no hemorrhage, areas of abnormal attenuation, or mass effect. A presumptive clinical diagnosis of right middle cerebral artery (MCA) ischemic stroke was made. After exclusion criteria for thrombolysis were ruled out, the patient received 90 mg of rt-PA intravenously at 65 minutes from emergency department arrival and 1 hour and 45 minutes from symptom onset per standard protocol. He experienced a subsequent dramatic clinical improvement with recovery of speech, sensation, and motor function to 5/5 in the left lower extremity and 4/5 in the left upper extremity. Brain magnetic resonance (MR) imaging/MR angiography without contrast at 12 hours revealed a wedge-shaped area of increased diffusion-weighted signal in the right frontoparietal region consistent with an acute cerebral infarct and several other small areas of increased signal consistent with shower emboli (Fig 1). Urgent transesophageal echocardiogram demonstrated a large lobulated left atrial mass, prolapsing into the left ventricle during diastole (Fig 2). Left ventricular function was normal. Urgent cardiac surgery at 48 hours from presentation was performed and intraoperatively a large, egg-shaped, encapsulated, 6.4- 3 5.0- 3 4.0-cm myxomatous left atrial mass (Fig 3) attached by a short stalk to the fossa ovalis was confirmed. After tumor resection and primary closure of the atrial septal defect, pathologic examination confirmed the diagnosis of atrial myxoma. The postoperative course was uneventful. The patient was discharged to rehabilitation. On 2-year follow-up he had only minimal residual left hand weakness.
399
Figure 1. MR diffusion-weighted imaging showing wedge-shaped area of increased diffusion-weighted signal in right frontoparietal region consistent with acute cerebral infarct and several other small areas of increased signal consistent with shower emboli.
Discussion Cardiac myxoma, the most common primary tumor of the heart, is believed to be a benign neoplasm of endocardial origin.6 It occurs in all age groups and is more prevalent in women.7-9 Most commonly it arises as an isolated tumor around the fossa ovalis in the left atrium.10 Clinical features are determined by tumor location, size, and mobility. There are no pathognomonic signs or symptoms suggesting the presence of atrial myxoma. In one series, however, younger age was significantly associated with neurologic signs, and sex was related to neurologic symptoms in men and systemic symptoms in women.11 Left atrial myxomas become symptomatic when they obstruct the mitral valve, embolize, or cause systemic effects. Cardiac symptoms are those of obstruction (dizziness, dyspnea on exertion, orthopnea, syncope, sudden death) occurring in 54% to 95% of patients3,8,9,11 and arrhythmias. Heart failure remains the most frequent cardiac manifestation.11 Systemic emboli are part of the presenting symptoms in 10% to 45% of patients.8,9,11,12 More than two thirds of myxomatous emboli migrate to the brain and cerebral infarction is the most frequent systemic event observed.4,12,13 Cerebral emboli may lead to pseudoaneurysms as delayed neurologic complications.14 Constitutional signs like fever, myalgias, muscle weakness, arthralgias, rash, weight loss, or fatigue resembling connective tissue disease complete the presenting picture in 50% to 90% of patients3,8,9,15,16 and may be related to effects of cytokine (e.g., interleukin-6) release.17 Diagnosis of atrial myxoma is made by echocardiography,18 which is noninvasive, is reliable, and does not entail any risk of tumor fragmentation and embolization.
C.D. NAGY ET AL.
400
Figure 2. Transesophageal echocardiogram showing large lobulated atrial myxoma.
Transthoracic echocardiogram has a sensitivity approaching 95%.19,20 Advantages of transesophageal echocardiogram are better specificity and a sensitivity approaching 100%.21,22 Currently, the decision for surgery is mainly based on echocardiographic evidence of disease. Other diagnostic methods include computed tomography and MR imaging. Their potential advantages over echocardiography are higher accuracy in assessing tumor attachment, endocardial site localization, tumor stalk description, and provision of sectional views of thoracic structures.23,24 Since the first reported description of a stroke caused by cardiac myxoma in 195225 there have been a handful of published case reports and series describing atrial myxoma and secondary ischemic strokes. Only 3 case reports mention the use of thrombolytics in acute strokes caused by cardiac myxoma. In two published cases thrombolytics were delivered by intra-arterial infusion
Figure 3. oma.
Operative photograph showing 6.4- 3 5.0- 3 4.0-cm atrial myx-
during cerebral angiography. In the first case, the patient presented with a right MCA infarct, and administration of urokinase at 3.5 hours from symptom onset resulted in partial recanalization without clinical improvement.26 The case was complicated by development of abdominal aorta occlusion distal to the renal arteries as a result of tumor embolization. Urgent thrombectomy was performed; however, the patient subsequently developed a large MCA infarct and died because of transtentorial herniation. In the second case, an acute stroke caused by a right MCA embolic occlusion was treated with rt-PA at 3 hours after symptom onset, achieving partial recanalization and improvement in motor deficits.27 No new intracranial hemorrhage was reported. In a third published case, an acute left frontal opercular infarct was treated with intravenous administration of rt-PA at 3 hours after symptom onset. Therapy was complicated by two hemorrhages remote from infarct location (one parenchymatous and one subarachnoid), presumably as a result of occult tumor emboli or microaneurysms.28 Subsequent catheter cerebral angiography, however, did not document any evidence of aneurysmal dilatation of the cerebral vessels. We report a case of successful intravenous thrombolysis in the setting of an acute ischemic stroke in a patient with previously undiagnosed atrial myxoma. Emboli associated with atrial myxoma consist of tumor tissue, thrombus, or a composite of both. Thrombotic emboli are rich in fibrin and amenable to thrombolysis. Vessels occluded by a composite embolus or thrombotic propagation of a myxomatous embolus may also recanalize by fibrinolysis. In contrast, emboli of only myxomatous tumor tissue would not be expected to be effectively treated by thrombolysis unless there was a superimposed in situ thrombosis. In acute strokes in patients with known history of atrial myxoma, cerebral angiography can aid in ruling out myxomatous thrombi.
INTRAVENOUS THROMBOLYSIS IN STROKE AS A RESULT OF MYXOMA
Intracranial aneurysms and pseudoaneurysms are a rare complication of myxomatous emboli.12 Although the pathogenesis is still speculative, pseudoaneurysm formation likely occurs secondary to myxomatous tumor invasion into the vessel wall leading to weakening of the artery. Intracranial hemorrhages may occur subsequent to rupture of myxomatous aneurysm. Therefore, some authors argue that thrombolytics should not be administered if pseudoaneurysms are visualized by angiogram because of this potential higher risk of bleeding.26,28 Definitive treatment for primary and secondary stroke prevention in patients with atrial myxoma is surgical tumor resection. In general, the outcome after cardiac myxoma resection is favorable. In one series of patients followed up during 15 years, the actuarial survival was 92% and event-free survival was 85.2%.29 In another series the 20-year survival was 85%.30 The recurrence rate of atrial myxoma is low (up to 5%).11 There are currently no guidelines or reliable studies on the role of perioperative anticoagulation in patients with atrial myxoma. Thrombolysis guidelines for acute stroke suggest withholding anticoagulation for at least 24 hours after thrombolytic infusion because of the risk of hemorrhagic conversion, which is the most feared consequence of lytic therapy for stroke. The risk of hemorrhagic transformation of ischemic infarcts after administration of intravenous heparin in studies of secondary stroke prevention increased 2- to 3-fold over use of no anticoagulation.31-33 Hence, it is recommended that anticoagulation with heparin for secondary stroke prevention as a result of emboli from atrial myxoma be used only if the estimated risk of recurrent stroke is considered to be higher than that of hemorrhagic conversion. Other anticoagulants such as low molecular–weight heparin have approximately the same risk of hemorrhagic transformation32 and, like unfractionated heparin, should be used with caution in patients with atrial myxoma after an acute ischemic event. The decision to anticoagulate after an acute stroke in the presence of atrial myxoma depends on clinical judgment of patient’s neurologic status, size of cerebral infarction, concurrent comorbidities, and previous treatments including thrombolysis. In our case, given the relatively large infarct in the MCA territory, the risk for hemorrhagic transformation was estimated to outweigh the benefit of anticoagulation for the short time until surgery. Therefore, the decision to withhold anticoagulation before surgical resection was made. In summary, this case is unique in several ways. First, the patient was young and relatively asymptomatic with a large MCA stroke. Based on national guidelines for stroke intervention, he received prompt lytic therapy, before the diagnosis of atrial myxoma was made. Most patients do not have an established diagnosis of cardiac myxoma at the time of stroke. It has been argued to consider known myxoma a relative contraindication to intra-
401
venous thrombolytic therapy for ischemic stroke because of a greater risk of hemorrhage from potential occult tumor emboli or microaneurysms. Our case demonstrates that, contrary to some expert opinion and prior published reports, systemic thrombolytic therapy can be safely and effectively used to treat acute ischemic strokes from atrial myxoma.
References 1. McAllister HA, Fenoglio JJ. Tumors of the cardiovascular system. Washington, DC: Armed Forces Institute of Pathology, 1978. 2. O’Neil MB, Rehl TM, Hurley EH. Cardiac myxomas: A clinical diagnostic challenge. Am J Surg 1979;138:68-74. 3. Reynen K. Cardiac myxomas. N Engl J Med 1995; 333:1610-1617. 4. Knepper LE, Biller J, Adams HP Jr, et al. Neurologic manifestations of atrial myxoma: A 12-year experience and review. Stroke 1988;19:1435-1440. 5. Damasio H, Seabra-Gomes R, da Silva JP, et al. Multiple cerebral aneurysms and cardiac myxoma. Arch Neurol 1975;32:269-270. 6. Johansson L. Histogenesis of cardiac myxomas: An immunohistochemical study of 19 cases including one with glandular structures and review of the literature. Arch Pathol Lab Med 1989;113:735-741. 7. Larsson S, Lepore V, Kennergren C. Atrial myxoma: Results of 25 years experience and review of the literature. Surgery 1989;105:695-698. 8. Markel ML, Waller BF, Armstrong WF. Cardiac myxoma: A review. Medicine (Baltimore) 1987;66:114-125. 9. St John Sutton MG, Mercier LA, Giuliani ER, et al. Atrial myxomas: A review of clinical experience in 40 patients. Mayo Clin Proc 1980;55:371-376. 10. Fine G, Morales A, Horn RC. Cardiac myxoma: A morphologic and histogenetic appraisal. Cancer 1986; 22:1156-1162. 11. Pinede L, Duhaut P, Loire R. Clinical presentation of left atrial myxoma: A series of 112 consecutive cases. Medicine (Baltimore) 2001;80:159-172. 12. Lee V, Connolly HM, Brown RD Jr. Central nervous system manifestations of cardiac myxoma. Arch Neurol 2007;64:1115-1120. 13. Sandok BA, Von Estroff I, Giulinai ER. CNS embolism due to atrial myxoma: Clinical features and diagnosis. Arch Neurol 1980;37:485-488. 14. Roeltgen DP, Weimer GR, Patterson LF. Delayed neurologic complications of left atrial myxoma. Neurology 1981;31:8-13. 15. Byrd WE, Mathews OP, Hunt RE. Left atrial myxoma presenting as a systemic vasculitis. Arthritis Rheum 1980; 23:240-243. 16. Le Cam MT, Duterque M. Myxome de l’oreillette: Manifestations cutanees. Ann Dermatol Venerol 1999; 126:32-34. 17. Parissis JT, Mentzikof D, Georgeopoulou M, et al. Correlation of interleukin-6 gene expression to immunologic features in patients with cardiac myxomas. J Interferon Cytokine Res 1996;16:589-593. 18. Mazer MS, Harrigan PR. Left ventricular myxoma: M-mode and two-dimensional echocardiographic features. Am Heart J 1982;104:875-877. 19. Nomeir AM, Watts LE, Seagle R, et al. Intracardiac myxomas: Twenty-year echocardiographic experience with
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20.
21.
22.
23.
24.
25.
26.
review of literature. Am J Soc Echocardiogr 1989; 2:139-150. Obeid AI, Marvasti M, Parker F, et al. Comparison of transthoracic and transesophageal echocardiography in diagnosis of left atrial myxoma. Am J Cardiol 1989; 63:1006-1008. Engberding R, Daniel WG, Erbel R, et al, and the European Cooperative Study Group. Diagnosis of heart tumors by transesophageal echocardiography: A multicenter study in 154 patients. Eur Heart J 1993; 14:1223-1228. Mugge A, Daniel WG, Haverich A, et al. Diagnosis of noninfective cardiac mass lesions by two-dimensional echocardiography: Comparison of the transthoracic and transesophageal approaches. Circulation 1991;83:70-78. Niehues B, Heuser L, Jansen W, et al. Noninvasive detection of intracardiac tumors by ultrasound and computed tomography. Cardiovasc Intervent Radiol 1983;6:30-36. Reddy DB, Jena A, Venugopal P. Magnetic resonance imaging in evaluation of left atrial masses: An in vitro and in vivo study. J Cardiovasc Surg 1994;35:289-294. Goldberg HP, Glenn F, Dotter CT, et al. Myxoma of the left atrium: Diagnosis made during life with operative and post-mortem findings. Circulation 1952;6:762-767. Bekavac I, Hanna JP, Wallace RC, et al. Intra-arterial thrombolysis of embolic proximal middle cerebral artery occlusion from presumed atrial myxoma. Neurology 1997;49:618-620.
27. Yamanome T, Yoshida K, Miura K, et al. Superselective fibrinolysis for a middle cerebral artery embolism caused by a left atrial myxoma: Case report. No Shinkei Geka 2000;28:653-658. 28. Chong JY, Vraniak P, Etienne M, et al. Intravenous thrombolytic treatment of acute ischemic stroke associated with left atrial myxoma: A case report. J Stroke Cerebrovasc Dis 2005;14:39-41. 29. Scrofani R, Carro C, Villa L, et al. Cardiac myxoma: Surgical results and 15-year clinical follow-up. Ital Heart J Suppl 2002;3:753-758. 30. Bjessmo S, Ivert T. Cardiac myxoma: 40 years’ experience in 63 patients. Ann Thorac Surg 1997;63:697-700. 31. International Stroke Trial Collaborative Group. The international stroke trial (IST): A randomized trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischemic stroke. Lancet 1997; 349:1569-1581. 32. CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST. Randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischemic stroke. Lancet 1997;349:1641-1649. 33. The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: A randomized controlled trial. JAMA 1998;279:1265-1272.
Safe and Effective Intravenous Thrombolysis for Acute Ischemic Stroke Caused by Left Atrial Myxoma Christian D. Nagy, MD,* Michael Levy, MD, PhD,† Thomas J. Mulhearn, IV, MD,‡ Maryam Shapland, MD,x Henry Sun, MD,* David D. Yuh, MD,// Dickson Cheung, MD,x and Nisha Chandra-Strobos, MD*
Atrial myxoma may be associated with syncope or sudden death attributed to leftsided cardiac outflow obstruction or embolization caused by tumor dislodgement or thrombus formation. Definitive treatment for primary and secondary stroke prevention is surgical resection. The role of thrombolysis in acute brain ischemia in patients with atrial myxoma is not defined. There are few data available regarding safety and efficacy of thrombolytic therapy in acute ischemic strokes caused by atrial myxoma. Prior case reports described partial success using intra-arterial local thrombolysis; however, this is invasive and can be associated with significant complications. A previously reported case of systemic thrombolysis resulted in development of cerebral hemorrhage. We describe a young man who presented with syncope and a dense stroke developing as a complication of atrial myxoma, followed by a remarkable recovery after treatment with intravenous recombinant tissue plasminogen activator and urgent cardiac surgery. Contrary to some expert opinion, systemic thrombolytic therapy may be safely and effectively used to treat acute ischemic strokes from atrial myxoma. Key Words: Stroke—atrial myxoma—thrombolysis— recombinant tissue plasminogen activator. Ó 2009 by National Stroke Association
Atrial myxoma is the most common primary heart tumor1 and presents an important diagnostic challenge.2,3 Cerebral infarction is a frequent complication of atrial
From the *Division of Cardiology, †Department of Neurology, xDepartment of Emergency Medicine, //Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland; and ‡Division of Cardiovascular Medicine, Duke University Medical Center, Durham, North Carolina. Received December 19, 2007; revision received November 16, 2008; accepted November 20, 2008. Address correspondence to Nisha Chandra-Strobos, MD, Johns Hopkins Bayview Medical Center, Department of Medicine, Division of Cardiology, 4940 Eastern Ave, Baltimore, MD 21224. E-mail: [email protected]. 1052-3057/$—see front matter Ó 2009 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2008.11.012
398
myxoma and, in addition to dyspnea and palpitation, the most common presentation leading to tumor detection. If the culprit is not identified and promptly removed, recurrent cerebral emboli before cardiac surgery can occur. Emboli from atrial myxoma are composed of thrombus, neoplasm, or a compound of both.4,5 The diagnosis is rarely known at stroke onset and the role of thrombolysis in brain ischemia in patients with atrial myxoma is unknown. We describe a young man who presented with syncope and a dense stroke developing as a complication of atrial myxoma, followed by a remarkable recovery after treatment with intravenous recombinant tissue plasminogen activator (rt-PA) and urgent surgery.
Case Report A previously healthy 26-year-old man was transported to the emergency department after sudden collapse
Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 5 (September-October), 2009: pp 398-402
INTRAVENOUS THROMBOLYSIS IN STROKE AS A RESULT OF MYXOMA
during a game of casual football. He had developed lightheadedness and subsequently fell to the ground. There was no trauma, loss of consciousness, chest pain, shortness of breath, palpitations, vertigo, or preceding aura. There was no seizurelike activity observed. On ambulance arrival he was found to have left-sided hemiparesis. Initial heart rate was 116/min and regular, blood pressure was 163/102 mm Hg, blood sugar was within normal limits, and Glasgow Coma Scale score was 15. On emergency department arrival no jugular venous distention was noted. Heart sounds were normal with an audible S4 and no murmurs, gallop, or rub. Chest and abdominal examination revealed normal findings. Extremities were well perfused. No skin lesions, bruises, or petechiae were identified. Neurologic examination revealed an alert and oriented man with mild dysarthria. Cranial nerve assessment showed left facial weakness presumably caused by upper motor neuron injury; strength was 0/5 in the left upper extremity and 3/5 in the left lower extremity; sensation was lost in the left arm and partially lost in the left leg; coordination was intact. The National Institutes of Health Stroke Scale score was 10. Laboratory work produced normal findings. Electrocardiogram demonstrated sinus tachycardia without left ventricular hypertrophy. Emergency head computed tomography scan without contrast showed no hemorrhage, areas of abnormal attenuation, or mass effect. A presumptive clinical diagnosis of right middle cerebral artery (MCA) ischemic stroke was made. After exclusion criteria for thrombolysis were ruled out, the patient received 90 mg of rt-PA intravenously at 65 minutes from emergency department arrival and 1 hour and 45 minutes from symptom onset per standard protocol. He experienced a subsequent dramatic clinical improvement with recovery of speech, sensation, and motor function to 5/5 in the left lower extremity and 4/5 in the left upper extremity. Brain magnetic resonance (MR) imaging/MR angiography without contrast at 12 hours revealed a wedge-shaped area of increased diffusion-weighted signal in the right frontoparietal region consistent with an acute cerebral infarct and several other small areas of increased signal consistent with shower emboli (Fig 1). Urgent transesophageal echocardiogram demonstrated a large lobulated left atrial mass, prolapsing into the left ventricle during diastole (Fig 2). Left ventricular function was normal. Urgent cardiac surgery at 48 hours from presentation was performed and intraoperatively a large, egg-shaped, encapsulated, 6.4- 3 5.0- 3 4.0-cm myxomatous left atrial mass (Fig 3) attached by a short stalk to the fossa ovalis was confirmed. After tumor resection and primary closure of the atrial septal defect, pathologic examination confirmed the diagnosis of atrial myxoma. The postoperative course was uneventful. The patient was discharged to rehabilitation. On 2-year follow-up he had only minimal residual left hand weakness.
399
Figure 1. MR diffusion-weighted imaging showing wedge-shaped area of increased diffusion-weighted signal in right frontoparietal region consistent with acute cerebral infarct and several other small areas of increased signal consistent with shower emboli.
Discussion Cardiac myxoma, the most common primary tumor of the heart, is believed to be a benign neoplasm of endocardial origin.6 It occurs in all age groups and is more prevalent in women.7-9 Most commonly it arises as an isolated tumor around the fossa ovalis in the left atrium.10 Clinical features are determined by tumor location, size, and mobility. There are no pathognomonic signs or symptoms suggesting the presence of atrial myxoma. In one series, however, younger age was significantly associated with neurologic signs, and sex was related to neurologic symptoms in men and systemic symptoms in women.11 Left atrial myxomas become symptomatic when they obstruct the mitral valve, embolize, or cause systemic effects. Cardiac symptoms are those of obstruction (dizziness, dyspnea on exertion, orthopnea, syncope, sudden death) occurring in 54% to 95% of patients3,8,9,11 and arrhythmias. Heart failure remains the most frequent cardiac manifestation.11 Systemic emboli are part of the presenting symptoms in 10% to 45% of patients.8,9,11,12 More than two thirds of myxomatous emboli migrate to the brain and cerebral infarction is the most frequent systemic event observed.4,12,13 Cerebral emboli may lead to pseudoaneurysms as delayed neurologic complications.14 Constitutional signs like fever, myalgias, muscle weakness, arthralgias, rash, weight loss, or fatigue resembling connective tissue disease complete the presenting picture in 50% to 90% of patients3,8,9,15,16 and may be related to effects of cytokine (e.g., interleukin-6) release.17 Diagnosis of atrial myxoma is made by echocardiography,18 which is noninvasive, is reliable, and does not entail any risk of tumor fragmentation and embolization.
C.D. NAGY ET AL.
400
Figure 2. Transesophageal echocardiogram showing large lobulated atrial myxoma.
Transthoracic echocardiogram has a sensitivity approaching 95%.19,20 Advantages of transesophageal echocardiogram are better specificity and a sensitivity approaching 100%.21,22 Currently, the decision for surgery is mainly based on echocardiographic evidence of disease. Other diagnostic methods include computed tomography and MR imaging. Their potential advantages over echocardiography are higher accuracy in assessing tumor attachment, endocardial site localization, tumor stalk description, and provision of sectional views of thoracic structures.23,24 Since the first reported description of a stroke caused by cardiac myxoma in 195225 there have been a handful of published case reports and series describing atrial myxoma and secondary ischemic strokes. Only 3 case reports mention the use of thrombolytics in acute strokes caused by cardiac myxoma. In two published cases thrombolytics were delivered by intra-arterial infusion
Figure 3. oma.
Operative photograph showing 6.4- 3 5.0- 3 4.0-cm atrial myx-
during cerebral angiography. In the first case, the patient presented with a right MCA infarct, and administration of urokinase at 3.5 hours from symptom onset resulted in partial recanalization without clinical improvement.26 The case was complicated by development of abdominal aorta occlusion distal to the renal arteries as a result of tumor embolization. Urgent thrombectomy was performed; however, the patient subsequently developed a large MCA infarct and died because of transtentorial herniation. In the second case, an acute stroke caused by a right MCA embolic occlusion was treated with rt-PA at 3 hours after symptom onset, achieving partial recanalization and improvement in motor deficits.27 No new intracranial hemorrhage was reported. In a third published case, an acute left frontal opercular infarct was treated with intravenous administration of rt-PA at 3 hours after symptom onset. Therapy was complicated by two hemorrhages remote from infarct location (one parenchymatous and one subarachnoid), presumably as a result of occult tumor emboli or microaneurysms.28 Subsequent catheter cerebral angiography, however, did not document any evidence of aneurysmal dilatation of the cerebral vessels. We report a case of successful intravenous thrombolysis in the setting of an acute ischemic stroke in a patient with previously undiagnosed atrial myxoma. Emboli associated with atrial myxoma consist of tumor tissue, thrombus, or a composite of both. Thrombotic emboli are rich in fibrin and amenable to thrombolysis. Vessels occluded by a composite embolus or thrombotic propagation of a myxomatous embolus may also recanalize by fibrinolysis. In contrast, emboli of only myxomatous tumor tissue would not be expected to be effectively treated by thrombolysis unless there was a superimposed in situ thrombosis. In acute strokes in patients with known history of atrial myxoma, cerebral angiography can aid in ruling out myxomatous thrombi.
INTRAVENOUS THROMBOLYSIS IN STROKE AS A RESULT OF MYXOMA
Intracranial aneurysms and pseudoaneurysms are a rare complication of myxomatous emboli.12 Although the pathogenesis is still speculative, pseudoaneurysm formation likely occurs secondary to myxomatous tumor invasion into the vessel wall leading to weakening of the artery. Intracranial hemorrhages may occur subsequent to rupture of myxomatous aneurysm. Therefore, some authors argue that thrombolytics should not be administered if pseudoaneurysms are visualized by angiogram because of this potential higher risk of bleeding.26,28 Definitive treatment for primary and secondary stroke prevention in patients with atrial myxoma is surgical tumor resection. In general, the outcome after cardiac myxoma resection is favorable. In one series of patients followed up during 15 years, the actuarial survival was 92% and event-free survival was 85.2%.29 In another series the 20-year survival was 85%.30 The recurrence rate of atrial myxoma is low (up to 5%).11 There are currently no guidelines or reliable studies on the role of perioperative anticoagulation in patients with atrial myxoma. Thrombolysis guidelines for acute stroke suggest withholding anticoagulation for at least 24 hours after thrombolytic infusion because of the risk of hemorrhagic conversion, which is the most feared consequence of lytic therapy for stroke. The risk of hemorrhagic transformation of ischemic infarcts after administration of intravenous heparin in studies of secondary stroke prevention increased 2- to 3-fold over use of no anticoagulation.31-33 Hence, it is recommended that anticoagulation with heparin for secondary stroke prevention as a result of emboli from atrial myxoma be used only if the estimated risk of recurrent stroke is considered to be higher than that of hemorrhagic conversion. Other anticoagulants such as low molecular–weight heparin have approximately the same risk of hemorrhagic transformation32 and, like unfractionated heparin, should be used with caution in patients with atrial myxoma after an acute ischemic event. The decision to anticoagulate after an acute stroke in the presence of atrial myxoma depends on clinical judgment of patient’s neurologic status, size of cerebral infarction, concurrent comorbidities, and previous treatments including thrombolysis. In our case, given the relatively large infarct in the MCA territory, the risk for hemorrhagic transformation was estimated to outweigh the benefit of anticoagulation for the short time until surgery. Therefore, the decision to withhold anticoagulation before surgical resection was made. In summary, this case is unique in several ways. First, the patient was young and relatively asymptomatic with a large MCA stroke. Based on national guidelines for stroke intervention, he received prompt lytic therapy, before the diagnosis of atrial myxoma was made. Most patients do not have an established diagnosis of cardiac myxoma at the time of stroke. It has been argued to consider known myxoma a relative contraindication to intra-
401
venous thrombolytic therapy for ischemic stroke because of a greater risk of hemorrhage from potential occult tumor emboli or microaneurysms. Our case demonstrates that, contrary to some expert opinion and prior published reports, systemic thrombolytic therapy can be safely and effectively used to treat acute ischemic strokes from atrial myxoma.
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