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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, in which neuropsychiatric manifestations are a common cause of significant morbidity. The American College of Rheumatology has identified 19 distinct neuropsychiatric syndromes associated with SLE, although the 1982 American College of Rheumatology classification criteria for SLE recognize only two: seizures and psychosis. Neurocognitive impairment (NCI) is one of the most common and clinically challenging manifestations of SLE, but its pathophysiology remains poorly understood. This Review examines the epidemiology and pathophysiology of NCI in children and adolescents with SLE, as well as the diagnostic and therapeutic approaches that are available for these patients. As few published studies specifically address NCI in pediatric SLE, new directions for research are also discussed.Published full-text, English-language articles for inclusion in this Review were identified from a search of the PubMed database from 1960 to June 2008. Search terms included: “systemic lupus erythematosus”, “pediatric” and “childhood” cross-referenced with “neurocognitive” and “neuropsychiatric”. Separate searches of “neuroimaging”, “pathogenesis” and “antibodies” cross-referenced with the previous searches were also performed. Emphasis was placed on discussing findings from prospective studies of children and adolescents, although retrospective and adult studies were also reviewed.