Neuropsychiatric systemic lupus erythematosus (NPSLE) is an emerging frontier in lupus care encompassing a wide spectrum of clinical manifestations among which cerebrovascular accidents, seizures, cognitive dysfunction, demyelinating syndromes, psychosis and optic neuritis/myelitis have received increased attention in recent years. Disruption of blood-brain barrier (BBB) facilitating entrance of neurotoxic antibodies into the central nervous system (CNS), neuroinflammation and cerebral ischemia are the key mechanisms. Although neuropsychiatric events are common in patients with systemic lupus erythematosus (SLE), less than one-third of these events can be directly attributed to SLE. Increased generalised SLE disease activity or damage, previous or concurrent major neuropsychiatric SLE (NPSLE) events, and persistently positive moderate-to-high antiphospholipid antibody titers are established risk factors, and their presence could facilitate proper attribution to the disease itself. Diagnostic evaluation is guided by the presenting manifestation; MRI is used to visualize brain or spinal pathologies. For neuropsychiatric events believed to reflect an immune or inflammatory process, or when these events occur in the context of active generalised disease, evidence (primarily from uncontrolled studies) supports the use of glucocorticoids alone or in combination with immunosuppressive therapy. Antiplatelet and/or anticoagulation therapy is recommended for NPSLE manifestations related to antiphospholipid antibodies, especially for thrombotic cerebrovascular disease.

Learning Objectives

• Describe the most common neuropsychiatric manifestations of SLE and their underlying pathophysiology and be able to attribute them to SLE or to other unrelated causes

• Distinguish between inflammatory vs thrombotic/embolic events

• Explain the use of the most appropriate immunosuppressive, anticoagulant/antiplatelet or adjunct therapies

• Describe the long-term prognosis and emerging therapies for patients with NPSLE