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Neuropsychiatric lupus: a mosaic of clinical presentations. Neuropsychiatric symptoms affect nearly half of the patients with systemic lupus erythematosus; however, the effect on disease severity, quality of life, and prognosis is tremendous. Symptoms of neuropsychiatric systemic lupus erythematosus may range from mild diffuse ones, to acute life threatening events. Although the underlying mechanisms are still largely unraveled, several pathogenic pathways are identified, such as antibody-mediated neurotoxicity, vasculopathy due to anti-phospholipid antibodies and other mechanisms, and cytokine-induced neurotoxicity. In the current review, we describe the old and the new regarding epidemiology, pathophysiology, diagnosis, and management of neuropsychiatric systemic lupus erythematosus. The possible link between neuropsychiatric symptoms and specific mechanisms may help to facilitate our understanding of the disease in the future, thus allowing for better treatment strategies.