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OBJECTIVES Advanced white matter hyperintensity (WMH) markers on brain MRI may help reveal underlying mechanisms and aid in the diagnosis of different phenotypes of systemic lupus erythematosus (SLE) patients experiencing neuropsychiatric (NP) manifestations. METHODS In this prospective cohort study we included a clinically well-defined cohort of 155 patients consisting of 38 patients with NPSLE (26 inflammatory and 12 ischaemic phenotype) and 117 non-NPSLE patients. Differences in 3 T MRI WMH markers (volume, type and shape) were compared between patients with NPSLE and non-NPSLE and between patients with inflammatory and ischaemic NPSLE by linear and logistic regression analyses corrected for age, sex and intracranial volume. RESULTS Compared with non-NPSLE (92% female; mean age 42 ± 13 years), patients with NPSLE (87% female; mean age 40 ± 14 years) showed a higher total WMH volume (B (95%-CI)): 0.46 (0.0 7 ↔0.86); p= 0.021), a higher periventricular/confluent WMH volume (0.46 (0.0 6 ↔0.86); p= 0.024), a higher occurrence of periventricular with deep WMH type (0.32 (0.1 3 ↔0.77); p= 0.011), a higher number of deep WMH lesions (3.06 (1.2 1 ↔4.90); p= 0.001) and a more complex WMH shape (convexity: -0.07 (-0.12↔-0.02); p= 0.011, concavity index: 0.05 (0.0 1 ↔0.08); p= 0.007). WMH shape was more complex in inflammatory NPSLE patients (89% female; mean age 39 ± 15 years) compared with patients with the ischaemic phenotype (83% female; mean age 41 ± 11 years) (concavity index: 0.08 (0.0 1 ↔0.15); p= 0.034). CONCLUSION We demonstrated that patients with NPSLE showed a higher periventricular/confluent WMH volume and more complex shape of WMH compared with non-NPSLE patients. This finding was particularly significant in inflammatory NPLSE patients, suggesting different or more severe underlying pathophysiological abnormalities.

Neuropsychiatric systemic lupus erythematosus is associated with a distinct type and shape of cerebral white matter hyperintensities