Distinctive cerebral small vessel disease patterns are associated with ischemic stroke in systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) increases the risk of ischemic stroke (IS) and cerebral small vessel disease (CSVD) through a unique interplay of cardiovascular and immune-mediated mechanisms. There is an unmet need of predictors of IS risk and of characterization of the distinctive features of CSVD in patients with SLE. Objectives To assess if CSVD is more extensive in patients with SLE and ischemic stroke (IS+) than in those without (IS-); to identify distinctive neuroimaging features of CSVD in patients with SLE. Methods This observational study, conducted at an academic referral center in São Paulo, Brazil, included SLE patients who underwent brain MRI between 2010 and 2021. Two neuroradiologists, blinded to clinical data, reached a consensus on the summary CSVD score, that consists of microbleeds, lacunes of presumed vascular origin, enlarged perivascular spaces, and white matter hyperintensities of presumed vascular origin. Logistic regression was performed with IS as the dependent variable. Results We included 106 patients, 53 IS+ and 53 IS- (median age: 41; interquartile range, 34;51 years; 92% women). The summary CSVD score was independently associated with the IS + group (OR 3.83, 95% CI 1.73 – 9.87, p = 0.002), even after adjusting for age, hypertension, secondary antiphospholipid syndrome, and use of antimalarial drugs. Microbleeds predominated in cortical regions (23/24, 92%), lacunes in the basal ganglia (10/16, 63%) and white matter hyperintensities in the deep white matter (47/59, 80%). Conclusion CSVD was more frequent in IS+ than in IS-, highlighting the need for prospective studies in SLE to test CSVD as a biomarker of IS risk. Microbleeds predominated in the cortical region, different from reports of age-related and hypertension-associated CSVD.