Heterogeneity of Stroke in Patients with Systemic Lupus Erythematosus

Abstract

Objective The underlying pathophysiology varies according to stroke subtype. However, stroke heterogeneity among patients with systemic lupus erythematosus (SLE) remains unstudied. We hypothesized that the contribution of SLE to stroke might vary according to its subtype and investigated the associations of SLE and various stroke subtypes. Methods Diagnostic codes and electronic medical records were used to identify 70 patients with SLE who developed acute cerebral infarction or intracerebral hemorrhaging at four tertiary referral hospitals between 2008 and 2018. Intracerebral hemorrhaging was classified as lobar or deep, while cerebral infarction was classified according to the SSS-TOAST criteria. Physician notes were used to identify SLE activity, and their prevalences were compared among stroke subtypes. Outcomes were collected from the patients' medical records. Results The most common stroke subtype in patients with SLE was that of undetermined causes (31%), followed by small artery occlusion (16%), cardioaortic embolism (13%), other causes (11%), lobar hemorrhaging (10%), deep hemorrhaging (10%), and large artery atherosclerosis (9%). Stroke onset occurred during a period of high SLE activity in 21 patients (30%). The proportion of patients with high SLE activity varied according to stroke subtype (p=0.039) and was highest for cerebral infarction with undetermined causes. Stroke recurrence or death was observed in 40% of patients within 5 years after the initial stroke onset. Conclusion The contributions of SLE to stroke varied significantly according to the stroke subtype. Given the unfavorable prognosis, close stroke subtype-specific observation by rheumatologists and stroke specialists is recommended after stroke events.

Keywords: antiphospholipid syndrome; cerebrovascular disease; lupus; prognosis; stroke; thrombosis.

Figure 1.

Study flowchart. CVD: cerebrovascular disease, NPSLE: neuropsychiatric systemic SLE, SLE: systemic lupus erythematosus

Figure 2.

Representative images of each stroke subtype in patients with systemic lupus erythematosus. (A) Proportions of each subtype. (B) Lobar hemorrhaging observed using non-contrast computed tomography (CT) and T2* images in a man with a history of antiphospholipid syndrome. (C) Deep hemorrhaging observed using non-contrast CT and T2* images in a woman with hypertension. (D-H) Cerebral infarction observed using diffusion-weighted images and magnetic resonance angiography. (D) The right internal carotid artery terminal branch was severely stenosed (arrow), and infarcts were located in the watershed area. (E) The right internal carotid was occluded and not visible (arrowheads). (F) Small artery occlusion in a man with diabetes mellitus. (G) Cerebral infarction after coronary angiography. (H) Scattered subcortical cerebral infarctions were observed without large-artery lesions.

Figure 3.

Patients with high systemic lupus erythematosus activity and prediction scores according to stroke subtype. (A) The number of patients with and without high SLE activity according to stroke subtype (21). (B) The prediction scores according to stroke subtype, with the boxes indicating the interquartile ranges. SLE: systemic lupus erythematosus, SAO: small artery occlusion, CAE: cardioaortic embolism, LAA: large artery atherosclerosis

Figure 4.

Serum concentrations of complement C3, C4, CH50, anti-dsDNA antibodies, and CRP according to stroke subtype. The serum concentrations of (A) C3, (B) C4, (C) CH50, (D) anti-dsDNA antibodies, and (E) CRP are shown according to stroke subtype. No significant associations of the marker concentrations with the stroke subtypes (p=0.86, p=0.31, p=0.25, p=0.157, and p=0.69) were found. Twelve values were missing for C3, 13 values were missing for C4, 16 values were missing for CH50, and 16 values were missing for anti-dsDNA antibodies. The boxes indicate the interquartile ranges. CRP: C-reactive protein, SAO: small artery occlusion, CAE: cardioaortic embolism, anti-dsDNA: anti-double stranded DNA, LAA: large artery atherosclerosis

Figure 5.

Kaplan-Meier curves for the cumulative risks of stroke or death (A) and stroke alone (B).