Basilar artery thrombosis in the setting of antiphospholipid syndrome Amin F. Saad, MD, Larry T. Nickell, MD, R. Evans Heithaus, MD, Sadat A. Shamim, MD, Michael J. Opatowsky, MD, MBA, and Kennith F. Layton, MD, MS
Antiphospholipid syndrome is an autoimmune disorder characterized by arterial or venous thrombosis, recurrent first-trimester pregnancy loss, and multiple additional clinical manifestations. We describe a man with severe atherosclerotic basilar artery stenosis and superimposed in situ thrombus who was found to have antiphospholipid syndrome.
CASE REPORT A 44-year-old male heavy smoker presented to the emergency department following the acute onset of left-sided weakness while at work. The patient had no history of hypertension, hyperlipidemia, diabetes, or obesity. No personal or family history of deep venous thrombosis or hypercoagulable disorder was present. Noncontrast head computed tomography (CT) and CT angiography revealed severe distal basilar artery stenosis (Figure 1). Emergent intravenously administered tissue plasminogen activator (tPA) thrombolytic therapy provided brief improvement followed by worsening left-sided weakness. Digital subtraction angiography confirmed the CT angiography findings. Intraarterial tPA was administered into the region of severe atherosclerotic stenosis and presumed in situ thrombus approximately 3 hours after intravenous tPA with slight improvement in the size of the lumen and contrast flow. The following day, magnetic resonance imaging (MRI) revealed acute ischemic change within the rostral pons and midbrain (Figure 2). Two days after admission, the patient’s neurologic status began to decline further, with interval loss of right upper and lower extremity motor function as well as severely dysarthric bulbar speech. Emergent repeat digital subtraction angiography with basilar artery endovascular stenting was performed (Figure 3). A hypercoagulability clinical evaluation revealed significantly elevated anticardiolipin antibodies (aCL) (IgG 31.9, IgM 66.2) and positive lupus-like anticoagulant. The patient received systemic anticoagulation with heparin followed by transition to warfarin. Aspirin was also initiated. The patient required tracheostomy and percutaneous gastrostomy. His right-sided weakness improved soon after stenting, and his dysarthric speech improved more gradually. The patient tolerated decannulation of his tracheostomy prior to discharge and was tolerating a dysphagia diet per speech 210
therapy recommendations. He was discharged to a skilled nursing facility with a residual neurologic deficit of 4/5 right upper and lower extremity strength, 2/5 left upper extremity strength, and 0/5 left lower extremity strength. DISCUSSION Antiphospholipid syndrome (APS) is associated with persistently positive antiphospholipid antibodies (aPL), most commonly aCL and lupus-like anticoagulant (1). In the absence of an underlying connective tissue disorder, the syndrome is referred to as primary APS, while secondary APS is most commonly seen associated with systemic lupus erythematosus. Diverse neurological manifestations of APS include cerebrovascular disease (stroke, transient ischemic attack, and venous thrombosis) in addition to a multiple sclerosis–like syndrome, seizures, migraine headaches, and cognitive dysfunction (1, 2). These symptoms are thought to reflect manifestations of hypercoagulability-induced ischemia of neural tissue and possibly direct actions of aPL. Experimental and clinical data have suggested an association of APS with atherosclerosis. Endothelial dysfunction, oxidative stress, platelet activation, and increased cell adhesion molecules are common to both diseases (3). Premature atherosclerosis may be the first clinical manifestation of APS, and in a case such as this where age-accelerated atherosclerosis is seen with superimposed thrombosis and subsequent rethrombosis, a hypercoagulable state such as APS should be considered. In a low-density lipoprotein receptor knockout mouse model with aCL induced by immunization with human aCL from an APS patient, enhanced atherogenesis has been observed (3). Endothelial dysfunction has been demonstrated using positron emission tomography in patients with APS (3). The treatment of patients with APS and thrombotic events is based on guidelines for venous thrombosis and ischemic From the Departments of Diagnostic Radiology (Saad, Nickell, Heithaus), Neurointerventional Radiology (Opatowsky, Layton), and Neurology (Shamim), Baylor University Medical Center at Dallas. Corresponding author: Amin F. Saad, MD, Department of Diagnostic Radiology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2014;27(3):210–212
a
b
c
Figure 1. (a) Coronal maximum intensity projection (MIP) reformatted image from the initial CT angiography demonstrates severe stenosis of the distal basilar artery (arrow). (b) Frontal and (c) lateral projections from the initial digital subtraction angiography following a right vertebral artery injection also reveal severe distal basilar artery stenosis (arrows).
stroke. The Antiphospholipid Antibodies and Stroke Study showed no difference between aspirin therapy and warfarin; however, in patients with severe thrombotic central nervous system manifestations, long-term treatment with warfarin has been recommended (1). Statins may be beneficial in the reduction of aPL-induced endothelial cell activation and intracellular signaling (1, 2). Basilar thrombosis is a neurologically devastating condition, with considerable mortality as well as frequently devastating neurologic outcomes to include the so-called “locked in” syndrome. Complete recanalization can be
a
achieved in about 60% of patients. Survival rates in patients undergoing thrombolysis alone range from only 30% to 60% (4). Revascularization is strongly linked to improved clinical outcomes (5). Thrombolysis alone may be unable to achieve revascularization particularly in the setting of underlying atherosclerosis, and a residual highgrade stenosis may increase the risk of reocclusion (6). In the series reported by Shi et al, successful stent placement was achieved in 90% of patients following intraarterial thrombolysis (6). Stenting in the setting of APL has not been previously described.
b
Figure 2. (a) Axial diffusion trace image from the initial MRI demonstrates cytotoxic edema compatible with acute infarction within the left paramedian rostral pons (arrow). (b) Axial T2-weighted MR image demonstrates edema corresponding to the region of infarction (arrow). Note the absence of normal basilar artery flow–related signal loss compatible with slow flow or vascular occlusion (arrowhead). July 2014
Basilar artery thrombosis in the setting of antiphospholipid syndrome
211
a
b
c
Figure 3. (a) Lateral projection from the digital subtraction angiography (DSA) following a right vertebral artery injection reveals deployment of the stent within the distal basilar artery and resultant resolution of the stenosis. (b) A frontal projection from the postprocedural DSA shows correction of the stenosis. (c) Axial T2-weighted image following endovascular stenting demonstrates normal flow-related signal within the basilar artery (arrow). Evolving edema in the region of infarction is present (arrowhead).
1. 2. 3. 4.
212
Mayer M, Cerovec M, Rados M, Cikes N. Antiphospholipid syndrome and central nervous system. Clin Neurol Neurosurg 2010;112(7):602–608. Arnson Y, Shoenfeld Y, Alon E, Amital H. The antiphospholipid syndrome as a neurological disease. Semin Arthritis Rheum 2010;40(2):97–108. Jara LJ, Medina G, Vera-Lastra O. Systemic antiphospholipid syndrome and atherosclerosis. Clin Rev Allergy Immunol 2007;32(2):172–177. Eberhardt O, Naegele T, Raygrotzki S, Weller M, Ernemann U. Stenting of vertebrobasilar arteries in symptomatic atherosclerotic disease
5.
6.
and acute occlusion: case series and review of the literature. J Vasc Surg 2006;43(6):1145–1154. Schulte-Altedorneburg G, Hamann GF, Mull M, Kühne D, Liebetrau M, Weber W, Brückmann H, Mayer TE. Outcome of acute vertebrobasilar occlusions treated with intra-arterial fibrinolysis in 180 patients. AJNR Am J Neuroradiol 2006;27(10):2042–2047. Shi M, Wang S, Zhu H, Feng J, Wu J. Emergent stent placement following intra-arterial thrombolysis for the treatment of acute basilar artery occlusion. J Clin Neurosci 2012;19(1):152–154.
Baylor University Medical Center Proceedings
Volume 27, Number 3
Antiphospholipid syndrome is an autoimmune disorder characterized by arterial or venous thrombosis, recurrent first-trimester pregnancy loss, and multiple additional clinical manifestations. We describe a man with severe atherosclerotic basilar artery stenosis and superimposed in situ thrombus who was found to have antiphospholipid syndrome.
CASE REPORT A 44-year-old male heavy smoker presented to the emergency department following the acute onset of left-sided weakness while at work. The patient had no history of hypertension, hyperlipidemia, diabetes, or obesity. No personal or family history of deep venous thrombosis or hypercoagulable disorder was present. Noncontrast head computed tomography (CT) and CT angiography revealed severe distal basilar artery stenosis (Figure 1). Emergent intravenously administered tissue plasminogen activator (tPA) thrombolytic therapy provided brief improvement followed by worsening left-sided weakness. Digital subtraction angiography confirmed the CT angiography findings. Intraarterial tPA was administered into the region of severe atherosclerotic stenosis and presumed in situ thrombus approximately 3 hours after intravenous tPA with slight improvement in the size of the lumen and contrast flow. The following day, magnetic resonance imaging (MRI) revealed acute ischemic change within the rostral pons and midbrain (Figure 2). Two days after admission, the patient’s neurologic status began to decline further, with interval loss of right upper and lower extremity motor function as well as severely dysarthric bulbar speech. Emergent repeat digital subtraction angiography with basilar artery endovascular stenting was performed (Figure 3). A hypercoagulability clinical evaluation revealed significantly elevated anticardiolipin antibodies (aCL) (IgG 31.9, IgM 66.2) and positive lupus-like anticoagulant. The patient received systemic anticoagulation with heparin followed by transition to warfarin. Aspirin was also initiated. The patient required tracheostomy and percutaneous gastrostomy. His right-sided weakness improved soon after stenting, and his dysarthric speech improved more gradually. The patient tolerated decannulation of his tracheostomy prior to discharge and was tolerating a dysphagia diet per speech 210
therapy recommendations. He was discharged to a skilled nursing facility with a residual neurologic deficit of 4/5 right upper and lower extremity strength, 2/5 left upper extremity strength, and 0/5 left lower extremity strength. DISCUSSION Antiphospholipid syndrome (APS) is associated with persistently positive antiphospholipid antibodies (aPL), most commonly aCL and lupus-like anticoagulant (1). In the absence of an underlying connective tissue disorder, the syndrome is referred to as primary APS, while secondary APS is most commonly seen associated with systemic lupus erythematosus. Diverse neurological manifestations of APS include cerebrovascular disease (stroke, transient ischemic attack, and venous thrombosis) in addition to a multiple sclerosis–like syndrome, seizures, migraine headaches, and cognitive dysfunction (1, 2). These symptoms are thought to reflect manifestations of hypercoagulability-induced ischemia of neural tissue and possibly direct actions of aPL. Experimental and clinical data have suggested an association of APS with atherosclerosis. Endothelial dysfunction, oxidative stress, platelet activation, and increased cell adhesion molecules are common to both diseases (3). Premature atherosclerosis may be the first clinical manifestation of APS, and in a case such as this where age-accelerated atherosclerosis is seen with superimposed thrombosis and subsequent rethrombosis, a hypercoagulable state such as APS should be considered. In a low-density lipoprotein receptor knockout mouse model with aCL induced by immunization with human aCL from an APS patient, enhanced atherogenesis has been observed (3). Endothelial dysfunction has been demonstrated using positron emission tomography in patients with APS (3). The treatment of patients with APS and thrombotic events is based on guidelines for venous thrombosis and ischemic From the Departments of Diagnostic Radiology (Saad, Nickell, Heithaus), Neurointerventional Radiology (Opatowsky, Layton), and Neurology (Shamim), Baylor University Medical Center at Dallas. Corresponding author: Amin F. Saad, MD, Department of Diagnostic Radiology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2014;27(3):210–212
a
b
c
Figure 1. (a) Coronal maximum intensity projection (MIP) reformatted image from the initial CT angiography demonstrates severe stenosis of the distal basilar artery (arrow). (b) Frontal and (c) lateral projections from the initial digital subtraction angiography following a right vertebral artery injection also reveal severe distal basilar artery stenosis (arrows).
stroke. The Antiphospholipid Antibodies and Stroke Study showed no difference between aspirin therapy and warfarin; however, in patients with severe thrombotic central nervous system manifestations, long-term treatment with warfarin has been recommended (1). Statins may be beneficial in the reduction of aPL-induced endothelial cell activation and intracellular signaling (1, 2). Basilar thrombosis is a neurologically devastating condition, with considerable mortality as well as frequently devastating neurologic outcomes to include the so-called “locked in” syndrome. Complete recanalization can be
a
achieved in about 60% of patients. Survival rates in patients undergoing thrombolysis alone range from only 30% to 60% (4). Revascularization is strongly linked to improved clinical outcomes (5). Thrombolysis alone may be unable to achieve revascularization particularly in the setting of underlying atherosclerosis, and a residual highgrade stenosis may increase the risk of reocclusion (6). In the series reported by Shi et al, successful stent placement was achieved in 90% of patients following intraarterial thrombolysis (6). Stenting in the setting of APL has not been previously described.
b
Figure 2. (a) Axial diffusion trace image from the initial MRI demonstrates cytotoxic edema compatible with acute infarction within the left paramedian rostral pons (arrow). (b) Axial T2-weighted MR image demonstrates edema corresponding to the region of infarction (arrow). Note the absence of normal basilar artery flow–related signal loss compatible with slow flow or vascular occlusion (arrowhead). July 2014
Basilar artery thrombosis in the setting of antiphospholipid syndrome
211
a
b
c
Figure 3. (a) Lateral projection from the digital subtraction angiography (DSA) following a right vertebral artery injection reveals deployment of the stent within the distal basilar artery and resultant resolution of the stenosis. (b) A frontal projection from the postprocedural DSA shows correction of the stenosis. (c) Axial T2-weighted image following endovascular stenting demonstrates normal flow-related signal within the basilar artery (arrow). Evolving edema in the region of infarction is present (arrowhead).
1. 2. 3. 4.
212
Mayer M, Cerovec M, Rados M, Cikes N. Antiphospholipid syndrome and central nervous system. Clin Neurol Neurosurg 2010;112(7):602–608. Arnson Y, Shoenfeld Y, Alon E, Amital H. The antiphospholipid syndrome as a neurological disease. Semin Arthritis Rheum 2010;40(2):97–108. Jara LJ, Medina G, Vera-Lastra O. Systemic antiphospholipid syndrome and atherosclerosis. Clin Rev Allergy Immunol 2007;32(2):172–177. Eberhardt O, Naegele T, Raygrotzki S, Weller M, Ernemann U. Stenting of vertebrobasilar arteries in symptomatic atherosclerotic disease
5.
6.
and acute occlusion: case series and review of the literature. J Vasc Surg 2006;43(6):1145–1154. Schulte-Altedorneburg G, Hamann GF, Mull M, Kühne D, Liebetrau M, Weber W, Brückmann H, Mayer TE. Outcome of acute vertebrobasilar occlusions treated with intra-arterial fibrinolysis in 180 patients. AJNR Am J Neuroradiol 2006;27(10):2042–2047. Shi M, Wang S, Zhu H, Feng J, Wu J. Emergent stent placement following intra-arterial thrombolysis for the treatment of acute basilar artery occlusion. J Clin Neurosci 2012;19(1):152–154.
Baylor University Medical Center Proceedings
Volume 27, Number 3
