Pathogenesis of neurocognitive and neuropsychiatric manifestations in childhood-onset lupus: an overview

Abstract

This review explores current understanding of neuropsychiatric systemic lupus erythematosus (NPSLE) of childhood onset, in particular neurocognitive impairment. As yet, fewer studies have focused on childhood onset NPSLE compared to adult onset NPSLE and diagnosis still involves the 1999 American College of Rheumatology case definitions of neuropsychiatric syndromes, which were developed for adults. Although a validated core set of neuropsychometric tests exist for childhood onset NPSLE, these still have limitations and possible biomarkers and newer neuroimaging modalities remain mostly experimental. Important differences exist between childhood and adult onset SLE and specifically with NPSLE, outlined in this review. Normal adolescent brain development also involves significant differences from adults, particularly in executive function and social cognition. These issues may impact on the pathogenesis of NPSLE during this vulnerable period and also influence their management options.

Cognitive dysfunction in patients with Systemic Lupus Erythematosus

“…Other antibodies with pathogenic relevance to cognitive dysfunction include anti-cardiolipin antibodies (ACL), anti-neuronal antibodies, anti-endothelial-cell antibodies (AECAs) and anti- Nedd5 C-ter antibodies 8-10. Patients with systemic lupus erythematosus (SLE) who have neuropsychiatric involvement were found to have significantly higher levels of matrix metalloproteinase-9 (MMP-9) in their serum and in cerebrospinal fluid (CSF), as compared to those without neuropsychiatric syndromes 11,12…”

Genetics in systemic lupus erythematosus: entering the borough of cardiovascular risk

“…In particular, genome-wide association studies (GWAS) revealed a strong association of multiple polymorphisms in key genes for interferon-α (IFNα) antiviral-like responses, antigen recognition and presentation, co-stimulation as well as B-and T-cell activation with the development of SLE (7,8). Nonetheless, the hereditary factors involved in the development of specific SLE manifestations have only recently begun to be defined and explored and stand as borderless boroughs of a larger city within the perimeter of general SLE susceptibility (9)(10)(11). Research in this field promises to define the mechanistic bases for prognostic profiling of patients with SLE and for individualised treatment choices.…”