Abstract

Introduction: Embolic stroke of undetermined source (ESUS) is a clinical paradigm that helps to classify and lead investigations into cryptogenic stroke. Diagnostic evaluation of ESUS involves investigating several potential etiologies of stroke. One such etiology includes antiphospholipid syndrome (APLS), a syndrome known to cause hypercoagulability. Clinical characteristics of primary APLS in ESUS have not been described. Methods: This is an IRB approved, retrospective study including patients from 2015-2020 who were seen at Mayo Clinic, were diagnosed with ESUS, and had APLS testing (anti-cardiolipin, beta-2 glycoprotein, or lupus anticoagulant). Baseline characteristics and radiographic features were collected and compared between patients who were and were not diagnosed with APLS, as well as between patients who were and were not APLS antibody positive. Results: Our study included 206 patients. Positive APLS antibody testing was seen in 21 (10%) patients. Of those patients, 8 (4%) received a formal diagnosis of APLS. Compared to controls, patients with positive APLS antibodies as well as those diagnosed with APLS were more likely to have a history of cancer (20 [11%] APLS antibody negative vs 7 [33%] APLS antibody positive p=0.004) (23 [12%] APLS diagnosis negative vs 4 [50%] APLS diagnosis p=0.002). Mean age in primary APLS was greater, 57 years old APLS antibody negative vs 69 years old APLS antibody positive (p<0.001) and 58 years old APLS diagnosis negative vs 75 years old APLS diagnosis (p=0.001) (Table 1). Regressions analyses examining infarct topography and rate of hemorrhagic transformation were non-significant between groups (p>0.1) Conclusion: APLS presenting as ESUS is associated with older age and history of malignancy. We speculate this finding may underscore the need to consider hypercoagulable conditions more broadly in stroke evaluations of older populations. Larger cohorts and longer follow up will be required to validate this observation.

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