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Neuropsychiatric systemic lupus erythematosus reconsidered

Nature Clinical Practice Rheumatology volume 4, pages 112–113 (2008)Cite this article

With the improved longevity of patients, it is increasingly appreciated that neuropsychiatric systemic lupus erythematosus (NPSLE) is a major cause of chronic disability, and that there are few specific therapies for many of the disease manifestations. In the 1999 consensus conference, the most recent of several consensus conferences on NPSLE, 19 specific syndromes affecting the neuromuscular junction, nerves, nerve roots, spinal cord, meninges or brain were designated to be potentially disease-related.1 This categorization considers stroke, seizure, movement disorders, transverse myelitis, insidiously progressive cognitive impairments, thought and mood disorders, headaches and neuropathy as a single disease entity, implying that there might be shared pathoetiologic features among these symptoms. Although the 1999 guidelines have been useful in the clinical setting, they have been less useful for dissecting pathological mechanisms of NPSLE or identifying appropriate therapies. Some impediments to the progression of our understanding of NPSLE seem to relate to the current classification of symptoms; therefore, it is timely to consider a reclassification of symptoms based on a pathoanatomic localization of the disease: vascular, central nervous system (CNS) and peripheral nervous system (PNS).

Vascular disease begins within vessels and does not involve a neuron-specific mechanism; injury depends on the location, duration and degree of vascular compromise. Vascular compromise of the brain or spinal cord from an embolus or thrombosis has been associated with antibodies that bind cardiolipin, phospholipids and other (as yet unidentified) molecules, activate a clotting cascade, and promote a hypercoagulable state.2 There is also evidence that these antibodies directly or indirectly activate endothelial cells. The etiology and treatment of thrombosis in the brain vasculature in NPSLE does not differ significantly from the etiology and treatment of thrombosis occurring elsewhere in patients with SLE. Although increases in intracranial pressure can be responsible, headaches in NPSLE are most often a result of vascular pathology: changes in vascular tone that result in headache are likely to relate to effects on endothelial and smooth muscle cells that are mediated by antibodies, cytokines or vasoactive molecules. A therapeutic approach to vascular NPSLE manifestations could involve deletion or inactivation of autoantibodies, interference with the clotting cascade, or inhibition of endothelial cell activation. Although rare, it should be noted that inflammation of small-to-medium-sized blood vessels in the CNS or PNS can also cause vascular disruption.

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Authors and Affiliations

  1. J Sánchez-Guerrero is Professor of Medicine at the Department of Immunology and Rheumatology, Instituto Nacional Nutrición, Mexico City, Mexico.,

    Jorge Sánchez-Guerrero

  2. C Aranow is an Investigator, M Mackay is an Investigator and B Diamond is Head of the Autoimmune Disease Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA.,

    Cynthia Aranow, Meggan Mackay & Betty Diamond

  3. B Volpe is Professor of Neurology at the Department of Neurology & Neuroscience, Weill Medical College of Cornell University, White Plains, NY, USA.,

    Bruce Volpe

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  1. Jorge Sánchez-Guerrero
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  2. Cynthia Aranow
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  3. Meggan Mackay
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  4. Bruce Volpe
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  5. Betty Diamond
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Correspondence to Bruce Volpe or Betty Diamond.

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Sánchez-Guerrero, J., Aranow, C., Mackay, M. et al. Neuropsychiatric systemic lupus erythematosus reconsidered. Nat Rev Rheumatol 4, 112–113 (2008). https://doi.org/10.1038/ncprheum0726

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