Cryptogenic Stroke in the Setting of Antiphospholipid Syndrome
Location
Moultrie, GA
Start Date
17-4-2026 12:00 PM
End Date
17-4-2026 1:00 PM
Description
Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with increased risk of thrombosis due to presence of procoagulatory antibodies. Despite well-established classification criteria, diagnosis is often delayed due to variable and frequently subtle clinical presentations. Affected individuals often present with nonspecific symptoms, including transient neurologic deficits, headaches, dizziness, or unexplained systemic complaints frequently attributed to etiologies other than an overt thromboembolic event.
APS affects approximately 40–50 individuals per 100,000 population, with peak onset between the ages of 30-50 years. Antiphospholipid antibodies have been identified in approximately 13–17% of patients with ischemic stroke under the age of 50, highlighting APS as an important cause of cryptogenic stroke.4 APS can be classified into four categories: thrombotic, obstetric, microvascular, and catastrophic. Clinical manifestations vary widely, ranging from thrombosis to severe obstetric complications such as recurrent pregnancy loss. The principal antibodies associated with APS include lupus anticoagulant (LA), anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies. Diagnostic classification requires persistent antibody positivity on two separate occasions at least 12 weeks apart. Certain individuals are at increased risk of thromboembolism including those with systemic rheumatic diseases, persistent LA positivity, double or triple aPL positivity, prior obstetric APS, or additional thrombotic risk factors. Among patients with systemic lupus erythematosus (SLE), lupus anticoagulant confers an approximately sixfold increased risk of venous thromboembolism, while anticardiolipin antibodies are associated with roughly a twofold increased risk.
We describe a patient who presented with intermittent dizziness, episodic bilateral jaw pain, predominant left-sided paresthesias, and intermittent chest pain with palpitations. Computed tomography of the head and neck without contrast failed to identify an etiology. Further assessment with transesophageal echocardiography did not reveal a cardioembolic source. Four months after symptom onset, the patient developed an acute ischemic stroke secondary to occlusion of the right middle cerebral artery M1 segment and was treated with intravenous thrombolysis. Follow-up magnetic resonance imaging demonstrated nonhemorrhagic ischemia involving the right basal ganglia and corona radiata. Despite secondary prevention with dual antiplatelet and statin therapy, the patient developed recurrent neurologic symptoms with imaging demonstrating an evolving subacute infarct of the corona radiata. Hypercoagulable work-up revealed elevated anticardiolipin IgG and anti-β2-glycoprotein I IgG antibodies, raising strong suspicion for APS. Anticoagulation with low-molecular-weight heparin was initiated and later transitioned to warfarin with a target international normalized ratio of 2–3 along with low-dose aspirin.
Management of APS centers on treatment with antiplatelet agents and systemic anticoagulation. In patients with high-risk aPL profiles, warfarin is generally favored over direct oral anticoagulants (DOAC) due to higher rates of recurrent arterial thrombosis observed with DOAC therapy. For venous thromboembolism, standard-intensity warfarin therapy with a target INR of 2–3 is recommended, while arterial events are often treated with warfarin in combination with low-dose aspirin. Patients with unprovoked APS-associated thrombosis generally require lifelong anticoagulation to prevent recurrence. This case highlights the insidious nature of APS and emphasizes the importance of maintaining a high index of suspicion in patients with cryptogenic stroke when recurrent neurologic symptoms occur despite initially unrevealing diagnostic evaluations.
Embargo Period
5-26-2026
Cryptogenic Stroke in the Setting of Antiphospholipid Syndrome
Moultrie, GA
Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with increased risk of thrombosis due to presence of procoagulatory antibodies. Despite well-established classification criteria, diagnosis is often delayed due to variable and frequently subtle clinical presentations. Affected individuals often present with nonspecific symptoms, including transient neurologic deficits, headaches, dizziness, or unexplained systemic complaints frequently attributed to etiologies other than an overt thromboembolic event.
APS affects approximately 40–50 individuals per 100,000 population, with peak onset between the ages of 30-50 years. Antiphospholipid antibodies have been identified in approximately 13–17% of patients with ischemic stroke under the age of 50, highlighting APS as an important cause of cryptogenic stroke.4 APS can be classified into four categories: thrombotic, obstetric, microvascular, and catastrophic. Clinical manifestations vary widely, ranging from thrombosis to severe obstetric complications such as recurrent pregnancy loss. The principal antibodies associated with APS include lupus anticoagulant (LA), anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies. Diagnostic classification requires persistent antibody positivity on two separate occasions at least 12 weeks apart. Certain individuals are at increased risk of thromboembolism including those with systemic rheumatic diseases, persistent LA positivity, double or triple aPL positivity, prior obstetric APS, or additional thrombotic risk factors. Among patients with systemic lupus erythematosus (SLE), lupus anticoagulant confers an approximately sixfold increased risk of venous thromboembolism, while anticardiolipin antibodies are associated with roughly a twofold increased risk.
We describe a patient who presented with intermittent dizziness, episodic bilateral jaw pain, predominant left-sided paresthesias, and intermittent chest pain with palpitations. Computed tomography of the head and neck without contrast failed to identify an etiology. Further assessment with transesophageal echocardiography did not reveal a cardioembolic source. Four months after symptom onset, the patient developed an acute ischemic stroke secondary to occlusion of the right middle cerebral artery M1 segment and was treated with intravenous thrombolysis. Follow-up magnetic resonance imaging demonstrated nonhemorrhagic ischemia involving the right basal ganglia and corona radiata. Despite secondary prevention with dual antiplatelet and statin therapy, the patient developed recurrent neurologic symptoms with imaging demonstrating an evolving subacute infarct of the corona radiata. Hypercoagulable work-up revealed elevated anticardiolipin IgG and anti-β2-glycoprotein I IgG antibodies, raising strong suspicion for APS. Anticoagulation with low-molecular-weight heparin was initiated and later transitioned to warfarin with a target international normalized ratio of 2–3 along with low-dose aspirin.
Management of APS centers on treatment with antiplatelet agents and systemic anticoagulation. In patients with high-risk aPL profiles, warfarin is generally favored over direct oral anticoagulants (DOAC) due to higher rates of recurrent arterial thrombosis observed with DOAC therapy. For venous thromboembolism, standard-intensity warfarin therapy with a target INR of 2–3 is recommended, while arterial events are often treated with warfarin in combination with low-dose aspirin. Patients with unprovoked APS-associated thrombosis generally require lifelong anticoagulation to prevent recurrence. This case highlights the insidious nature of APS and emphasizes the importance of maintaining a high index of suspicion in patients with cryptogenic stroke when recurrent neurologic symptoms occur despite initially unrevealing diagnostic evaluations.