Significance of cerebral microinfarcts in antiphospholipid syndrome: A population-based study

Background: Acute ischemic stroke (AIS) or transient ischemic attack (TIA) is the most common neurological manifestations of patients with antiphospholipid syndrome (APS). Incidental diffusion-weighted imaging (DWI) positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMI), are microscopic ischemic lesions, detectable on MRI for 10-14 days only. We aimed to look at the prevalence of acute incidental CMI in a cohort of patients with APS and their association with subsequent AIS or TIA. Methods: This is a population-based cohort study of adults with APS diagnosis using International Statistical Classification-9 (ICD-9) and supporting laboratory results between January 2014 and April 2020. We included any patient undergoing brain MRI (index event) during the year prior APS diagnosis or at any time point following diagnosis. Age-matched subjects with negative APS laboratory workup were used as a control group. In the first analysis, we compared acute incidental CMI prevalence in both groups. We then performed a second analysis among APS patients only, comparing patients with and without acute incidental CMI for AIS or TIA as the primary outcome. Cox proportional hazards models used to calculate hazards ratio (HR) and 4 years cumulative risk. Results: 292 patients were included, of which, 207 patients with APS. Thirteen patients with APS had acute incidental CMI on MRI (6.3%), compared with none in the control group (p = 0.013). Following multivariable analysis, APS was the sole factor associated with acute incidental CMI (p = 0.026). During a median follow-up of 4 years (IQR 3.5, 4) in patients with APS, following multivariable analysis, acute incidental CMI was associated with subsequent AIS or TIA (HR 6.73 [(95% CI, 1.96-23.11], p < 0.01). Conclusion: Acute incidental CMI are more common among patients with APS than in patients with negative APS tests, and are associated with subsequent AIS or TIA. Detecting acute incidental CMI in patients with APS may guide etiological workup and reevaluation of antithrombotic regimen.