NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS: DIAGNOSTIC AND TREATMENT CHALLENGES
Keywords:
Systemic lupus erythematosus, neuropsychiatric lupus, NPSLE, attribution, antiphospholipid antibodies, cognitive dysfunction, lupus psychosis, cerebrospinal fluid, neuroimaging, immunosuppression.Abstract
Background: Systemic lupus erythematosus (SLE) can affect the central and peripheral nervous systems through mechanisms that range from autoantibody-mediated neuronal injury and complement activation to thrombotic vasculopathy driven by antiphospholipid antibodies, producing a heterogeneous group of syndromes collectively termed neuropsychiatric SLE (NPSLE).
Methods: This narrative review synthesizes current evidence on the classification, pathogenesis, diagnostic work-up, and treatment of NPSLE, drawing on the 1999 American College of Rheumatology (ACR) case definitions and the 2010 and 2023 EULAR recommendations for the management of neuropsychiatric and general SLE manifestations.
Results: NPSLE encompasses 19 defined syndromes spanning diffuse and focal central nervous system disease and peripheral neuropathies, of which cerebrovascular disease, seizures, cognitive dysfunction, and mood disorders are the most frequent. No single test reliably attributes a neuropsychiatric event to lupus; diagnosis instead depends on a structured attribution process that excludes infectious, metabolic, and drug-related mimics and integrates autoantibody profiles, neuroimaging, cerebrospinal fluid analysis, and neuropsychological assessment. Treatment bifurcates according to the presumed mechanism: glucocorticoids and immunosuppressive agents for inflammatory manifestations believed to reflect active lupus, and antiplatelet or anticoagulant therapy for manifestations attributed to antiphospholipid-mediated thrombosis.
Conclusion: Accurate attribution remains the central diagnostic challenge in NPSLE, and mechanism-directed therapy — rather than a uniform escalation of immunosuppression — is essential to improving outcomes, including in resource-constrained healthcare settings such as Uzbekistan, where access to advanced neuroimaging and specific autoantibody assays may be limited.
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