Neuropsychiatric manifestations pose diagnostic and therapeutic challenges in systemic lupus erythematosus (SLE). We review recently published studies on the epidemiology, pathogenesis, neuroimaging, and treatment of NPSLE.
Generalized SLE activity or damage and antiphospholipid antibodies are identified as major risk factors for neuropsychiatric involvement. NPSLE patients have increased genetic burden and novel genomic approaches are expected to elucidate its pathogenesis. Animal data suggest that, in cases of disturbed blood–brain barrier, autoantibodies against the NR2 subunits of the N-methyl-D-aspartate receptor and 16/6 idiotype antibodies may cause diffuse neuropsychiatric manifestations through neuronal apoptosis or brain inflammation; data in humans are still circumstantial. In NPSLE, advanced neuroimaging uncovers structural and metabolic abnormalities in brain regions with normal appearance on conventional MRI. Treatment includes corticosteroids/immunosuppressants for inflammatory manifestations or generalized SLE activity, and antiplatelets/anticoagulation for manifestations related to antiphospholipid antibodies. In refractory cases, uncontrolled studies suggest a beneficial role of rituximab.
We have begun to better understand how brain-reactive autoantibodies, present in a proportion of SLE patients, can cause brain injury and diffuse NPSLE. Further testing will be required to determine the clinical utility of advanced neuroimaging. Controlled trials are needed to guide therapeutic decisions.
aRheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, Crete
bInstitute of Molecular Biology and Biotechnology, Foundation of Research and Technology – Hellas, Heraklion
cMedical School, National and Kapodistrian University of Athens
dBiomedical Research Foundation of the Academy of Athens, Athens, Greece
Correspondence to George K. Bertsias, MD, Rheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, 71 003 Voutes-Stavrakia, Iraklion, Greece. Tel: +30 2810 394635; fax: +30 2810 392024; e-mail: firstname.lastname@example.org