Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions

Abstract

The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood-brain barrier and autoantibody-mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE.

Structural and functional brain connectomes in patients with systemic lupus erythematosus

“…Several pathophysiological substrates, including microvasculopathy, autoantibodies and inflammatory mediators, might contribute to brain damage accumulation in SLE [1,5]. In our exploratory analyses, patients with SLE with ADNA autoantibodies showed more severe structural global and nodal abnormalities.…”

“…Several pathophysiological substrates, including microvasculopathy, autoantibodies and inflammatory mediators, might contribute to brain damage accumulation in SLE .…”

A Novel System to Categorize the Symptoms of Systemic Lupus Erythematosus

“…Any strategy for attribution, however, would be influenced by the conceptual framework and the amount and type of data that are available (54)(55)(56). In this regard, attribution of any symptom to SLE can be problematic in view of the nonspecific nature and lack of reliable biomarkers.…”

“…In this regard, attribution of any symptom to SLE can be problematic in view of the nonspecific nature and lack of reliable biomarkers. Any strategy for attribution, however, would be influenced by the conceptual framework and the amount and type of data that are available (54)(55)(56). Nevertheless, we would suggest that considering a symptom as a part of lupus rather than a comorbidity would enhance the priority placed on its evaluation and treatment and thereby increase the overall effectiveness of therapy, especially in terms of quality of life.…”

To Eat the Elephant

“…New dynamic contrast‐enhanced magnetic resonance imaging (MRI), functional MRI, positron emission tomography scanning, and analyses of brain anatomy and metabolism increase our ability to study normal and abnormal brain function . Improved technologies in the fields of molecular immunology, blood–brain barrier function, and cognitive function , and new concepts like microglial metabolism and pruning , are beginning to demystify the complexity of CNS SLE.…”