It is estimated that two thirds of neuropsychiatric (NP) manifestations in lupus are not directly related to active NP lupus but instead are a consequence of secondary causes such as drugs, infections, and hypertensive and metabolic complications in the setting of systemic lupus erythematosus (SLE). It is often difficult to distinguish clinically between primary central nervous system lupus and secondary causes of NP manifestations. In general, NPSLE has been reported to be a prognostic factor for a poor long-term outcome in lupus. Despite early recognition of the disease and aggressive therapeutic interventions, it is still frequently associated with increased mortality.