Progress in the Pathogenesis and Treatment of Neuropsychiatric Systemic Lupus Erythematosus

Abstract

Neuropsychiatric systemic lupus erythematosus (NPSLE) has a broad spectrum of subtypes with diverse severities and prognoses. Ischemic and inflammatory mechanisms, including autoantibodies and cytokine-mediated pathological processes, are key components of the pathogenesis of NPSLE. Additional brain-intrinsic elements (such as the brain barrier and resident microglia) are also important facilitators of NPSLE. An improving understanding of NPSLE may provide further options for managing this disease. The attenuation of neuropsychiatric disease in mouse models demonstrates the potential for novel targeted therapies. Conventional therapeutic algorithms include symptomatic, anti-thrombotic, and immunosuppressive agents that are only supported by observational cohort studies, therefore performing controlled clinical trials to guide further management is essential and urgent. In this review, we aimed to present the latest pathogenetic mechanisms of NPSLE and discuss the progress in its management.

A case report: Catatonic symptoms secondary to systemic lupus erythematosus with multiple infections: neuropsychiatric or “mimickers?”

“…[10] Certain clinical, laboratorial, and neuroradiological features are extremely helpful to assist in determining possible etiologies and the differential diagnosis. [11] More recently, different attribution models have been developed to help determine if the NP event is due to SLE, and some researchers have summarized the evaluation strategy for SLE patients presenting with new onset or worsening NP symptoms (Fig. 4).…”

New-onset acute psychosis as a manifestation of lupus cerebritis following concomitant COVID-19 infection and vaccination: a rare case report

“…Acute psychosis as the first and main presenting manifestation of SLE is rarely encountered in clinical practice [ 19 ]. The etiopathogenesis of psychosis due to neuro-lupus is multifactorial, yet complex and unclear [ 20 ]. The two main, and likely complementary proposed mechanisms are (1) autoimmune/ inflammatory and (2) ischemic or thrombotic pathways [ 20 , 21 ].…”

“…The etiopathogenesis of psychosis due to neuro-lupus is multifactorial, yet complex and unclear [ 20 ]. The two main, and likely complementary proposed mechanisms are (1) autoimmune/ inflammatory and (2) ischemic or thrombotic pathways [ 20 , 21 ]. The autoimmune-mediated neuro-inflammatory pathway involves an increased permeability of the blood-brain barrier, with neuronal autoantibodies intrathecal migration and intracranial generation of pro-inflammatory mediators (cytokines and others) [ 20 ].…”

Headache and systemic lupus erythematosus: A narrative review

“…In turn, the immune-mediated inflammatory mechanism predominantly involves other autoantibodies such as ribosomal anti-P, anti-NMDAR/NR2, and anti-endothelial cells, with the production of cytokines and pro-inflammatory mediators such as interleukin (IL)-6, IL-8, tumor necrosis factor-like weak inducer of apoptosis, monocyte chemoattractant protein-1, interferon gamma inducible protein-10, and others, associated with complement activation. 53 In these cases, blood-brain barrier dysfunction seems to play a key role, enabling the migration of autoantibodies to the central nervous system (CNS), resulting in cytotoxicity, apoptosis, and neuronal damage. This culminates in diffuse neurological events such as encephalopathy, psychosis, cognitive dysfunction, and acute confusional state.…”