Neuropsychiatric manifestations in systemic lupus erythematosus and antiphospholipid syndrome: pathophysiology and current insights

Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) and anti­phospholipid syndrome (APS) represent complex clinical challenges due to their diverse presentations and multifactorial pathogenesis. Neuropsychiatric SLE (NPSLE) affects approximately 30–40% of SLE patients, with symptoms ranging from cognitive dysfunction to severe conditions such as stroke, seizures, and psychosis. In APS, cerebrovascular events, including ischemic stroke and transient ischemic attacks, occur in ∼20% of patients, alongside non-thrombotic manifestations like migraine and chorea. The underlying mechanisms involve immune-mediated neuronal injury, vascular thrombosis, and neuroinflammation. In NPSLE, autoantibodies, inflammatory cytokines, and complement activation drive neuronal damage, while APS is primarily characterized by antiphospholipid antibody-mediated thrombosis, with additional direct neuronal effects. Advanced neuroimaging, including diffusion tensor imaging, functional MRI, and positron emission tomography, reveals subtle structural and functional brain alterations. Emerging biomarkers, such as neurofilament light chain and glial fibrillary acidic protein, show promise for detecting neural and glial injury. This review synthesizes current insights into the pathophysiology, diagnostic approaches to neuropsychiatric manifestations in SLE and APS, emphasizing the need for integrated clinical, imaging, and laboratory evaluations to improve diagnostic precision and patient outcomes.