systemic lupus erythematosus Cerebral Small Vessel Disease Burden Is Increased in Systemic Lupus Erythematosus

The inflammatory autoimmune disease systemic lupus erythematosus (SLE) can involve the brain, including increasing stroke risk for reasons that remain incompletely understood. Cerebral small vessel disease (SVD) is an intrinsic disorder of the brain’s perforating arterioles. Imaging features range from asymptomatic white matter hyperintensities (WMH) and other brain imaging biomarkers of SVD such as an increase in number and size of visible perivascular spaces (PVS) to symptomatic lacunar stroke, which accounts for ≈25% of ischemic strokes. Symptoms also include cognitive impairment and dementia, depression, and balance problems. In sporadic SVD, inflammation and cell infiltrates are seen in the perforating arteriolar walls, and microglial activation is seen in the perivascular tissue on pathology. The source of the inflammation is not known, whether intrinsic or triggered by systemic processes. However, consistent with an inflammatory component, SVD-related PVS are associated with raised plasma markers of inflammation in healthy older subjects. Also, C-reactive protein (CRP), a common plasma marker of inflammation, was associated with lacunar infarcts in a recent large (n=519) study, independent of age and vascular risk factors. Thus, factors that contribute to endothelial damage, such as immune complex formation and complement activation/ deposition, and occur in SLE might trigger cerebrovascular inflammation in SLE. We hypothesized that one explanation for increased stroke risk in patients with SLE could be via the effects of systemic inflammation on cerebral small vessel integrity. Our aims were to measure and compare imaging biomarkers of SVD Background and Purpose—Systemic lupus erythematosus (SLE) increases stroke risk, but the mechanism is uncertain. This study aimed to determine the association between SLE and features on neuroimaging of cerebral small vessel disease (SVD), a risk factor for stroke. Methods—Consecutive patients attending a clinic for SLE were recruited. All patients underwent brain magnetic resonance imaging; had blood samples taken for markers of inflammation, endothelial dysfunction, cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing. The data were compared with sexand age-matched healthy controls and patients with minor stroke. Features of SVD were measured, a total SVD score calculated, and associations sought with vascular risk factors, cognition, SLE activity, and disease duration. Results—Fifty-one SLE patients (age: 48.8 years; SD: 14.3 years) had a greater total SVD score compared with healthy controls (1 versus 0; P<0.0001) and stroke patients (1 versus 0; P=0.02). There were higher perivascular spaces and deep white matter hyperintensity scores and more superficial brain atrophy in SLE patients versus healthy controls. Despite fewer vascular risk factors than similarly aged stroke patients, SLE patients had similar or more of some SVD features. The total SVD score was not associated with SLE activity, cognition, disease duration, or any blood measure. Conclusions—In this data set, SLE patients had a high burden of SVD features on magnetic resonance imaging, particularly perivascular spaces. A larger longitudinal study is warranted to determine the causes of SVD features in SLE and clinical implications. (Stroke. 2016;47:2722-2728. DOI: 10.1161/STROKEAHA.116.014330.)