Key Points
-
Neuropsychiatric events are common in patients with systemic lupus erythematosus (SLE) but only one-third of such events are attributed directly to SLE
-
Autoimmune-mediated inflammatory injury and vascular injury are separate pathogenetic mechanisms responsible for neuropsychiatric SLE (NPSLE)
-
The diagnosis of NPSLE is determined primarily by clinical assessment
-
Investigations in support of the clinical diagnosis include measurement of autoantibodies, analysis of cerebrospinal fluid, electrophysiological studies, neuropsychological assessment and neuroimaging
-
Treatment options for NPSLE include addressing comorbidities, symptomatic therapies, immunosuppression and anticoagulation
Abstract
Nervous system involvement in systemic lupus erythematosus (SLE) can manifest as a range of neurological and psychiatric features, which are classified using the ACR case definitions for 19 neuropsychiatric syndromes. Approximately one-third of all neuropsychiatric syndromes in patients with SLE are primary manifestations of SLE-related autoimmunity, with seizure disorders, cerebrovascular disease, acute confusional state and neuropathy being the most common. Such primary neuropsychiatric SLE (NPSLE) events are a consequence either of microvasculopathy and thrombosis, or of autoantibodies and inflammatory mediators. Diagnosis of NPSLE requires the exclusion of other causes, and clinical assessment directs the selection of appropriate investigations. These investigations include measurement of autoantibodies, analysis of cerebrospinal fluid, electrophysiological studies, neuropsychological assessment and neuroimaging to evaluate brain structure and function. Treatment involves the management of comorbidities contributing to the neuropsychiatric event, use of symptomatic therapies, and more specific interventions with either anticoagulation or immunosuppressive agents, depending upon the primary immunopathogenetic mechanism. Although the prognosis is variable, studies suggest a more favourable outcome for primary NPSLE manifestations compared with neuropsychiatric events attributable to non-SLE causes.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Gladman, D. & Urowitz, M. B. in Rheumatology (ed. Hochberg, M. C.) 1359–1380 (Mosby, Toronto, 2003).
Cervera, R. et al. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore) 78, 167–175 (1999).
Jacobsen, S. et al. Mortality and causes of death of 513 Danish patients with systemic lupus erythematosus. Scand. J. Rheumatol. 28, 75–80 (1999).
Urowitz, M. B., Gladman, D. D., Abu-Shakra, M. & Farewell, V. T. Mortality studies in systemic lupus erythematosus. Results from a single center. III. Improved survival over 24 years. J. Rheumatol. 24, 1061–1065 (1997).
Ainiala, H. et al. Validity of the new American College of Rheumatology criteria for neuropsychiatric lupus syndromes: a population-based evaluation. Arthritis Rheum. 45, 419–423 (2001).
Brey, R. L. et al. Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology 58, 1214–1220 (2002).
Hanly, J. G., McCurdy, G., Fougere, L., Douglas, J. A. & Thompson, K. Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical significance. J. Rheumatol. 31, 2156–2162 (2004).
Sanna, G. et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J. Rheumatol. 30, 985–992 (2003).
Sibbitt, W. L. Jr et al. The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus. J. Rheumatol. 29, 1536–1542 (2002).
Boumpas, D. T. et al. Systemic lupus erythematosus: emerging concepts. Part 1: Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann. Intern. Med. 122, 940–950 (1995).
Sergent, J. S., Lockshin, M. D., Klempner, M. S. & Lipsky, B. A. Central nervous system disease in systemic lupus erythematosus. Therapy and prognosis. Am. J. Med. 58, 644–654 (1975).
Ainiala, H., Loukkola, J., Peltola, J., Korpela, M. & Hietaharju, A. The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 57, 496–500 (2001).
Estes, D. & Christian, C. L. The natural history of systemic lupus erythematosus by prospective analysis. Medicine (Baltimore) 50, 85–95 (1971).
Ginzler, E. M. et al. A multicenter study of outcome in systemic lupus erythematosus. I. Entry variables as predictors of prognosis. Arthritis Rheum. 25, 601–611 (1982).
Lee, P. et al. Systemic lupus erythematosus. A review of 110 cases with reference to nephritis, the nervous system, infections, aseptic necrosis and prognosis. Q. J. Med. 46, 1–32 (1977).
Bernatsky, S. et al. Mortality related to cerebrovascular disease in systemic lupus erythematosus. Lupus 15, 835–839 (2006).
Sibley, J. T., Olszynski, W. P., Decoteau, W. E. & Sundaram, M. B. The incidence and prognosis of central nervous system disease in systemic lupus erythematosus. J. Rheumatol. 19, 47–52 (1992).
Feinglass, E. J., Arnett, F. C., Dorsch, C. A., Zizic, T. M. & Stevens, M. B. Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine (Baltimore) 55, 323–339 (1976).
Kovacs, J. A., Urowitz, M. B. & Gladman, D. D. Dilemmas in neuropsychiatric lupus. Rheum. Dis. Clin. North Am. 19, 795–814 (1993).
[No authors listed] The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 42, 599–608 (1999).
Hanly, J. G. et al. Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: results from an international inception cohort study. Arthritis Rheum. 58, 843–853 (2008).
Hanly, J. G. et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum. 56, 265–273 (2007).
Hanly, J. G. et al. Short-term outcome of neuropsychiatric events in systemic lupus erythematosus upon enrollment into an international inception cohort study. Arthritis Rheum. 59, 721–729 (2008).
Hanly, J. G. et al. Prospective study of neuropsychiatric events in systemic lupus erythematosus. J. Rheumatol. 36, 1449–1459 (2009).
Hanly, J. G. et al. Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus. Ann. Rheum. Dis. 69, 529–535 (2010).
Hanly, J. G., Su, L., Omisade, A., Farewell, V. T. & Fisk, J. D. Screening for cognitive impairment in systemic lupus erythematosus. J. Rheumatol. 39, 1371–1377 (2012).
Hanly, J. G. in Systemic Lupus Erythematosus, 5th edn (ed. Lahita, R. G.) 727–746 (Elsevier, 2011).
Denburg, S. D. & Denburg, J. A. Cognitive dysfunction and antiphospholipid antibodies in systemic lupus erythematosus. Lupus 12, 883–890 (2003).
Hanly, J. G. & Liang, M. H. Cognitive disorders in systemic lupus erythematosus. Epidemiologic and clinical issues. Ann. NY Acad. Sci. 823, 60–68 (1997).
Ellis, S. G. & Verity, M. A. Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955–1977. Semin. Arthritis Rheum. 8, 212–221 (1979).
Johnson, R. T. & Richardson, E. P. The neurological manifestations of systemic lupus erythematosus. Medicine (Baltimore) 47, 337–369 (1968).
Weiner, S. M., Klein, R. & Berg, P. A. A longitudinal study of autoantibodies against central nervous system tissue and gangliosides in connective tissue diseases. Rheumatol. Int. 19, 83–88 (2000).
Bluestein, H. G., Williams, G. W. & Steinberg, A. D. Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus. Am. J. Med. 70, 240–246 (1981).
Zvaifler, N. J. & Bluestein, H. G. The pathogenesis of central nervous system manifestations of systemic lupus erythematosus. Arthritis Rheum. 25, 862–866 (1982).
Martinez-Cordero, E., Rivera Garcia, B. E. & Aguilar Leon, D. E. Anticardiolipin antibodies in serum and cerebrospinal fluid from patients with systemic lupus erythematosus. J. Investig. Allergol. Clin. Immunol. 7, 596–601 (1997).
Gono, T. et al. NR2-reactive antibody decreases cell viability through augmentation of Ca2+ influx in systemic lupus erythematosus. Arthritis Rheum. 63, 3952–3959 (2011).
DeGiorgio, L. A. et al. A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat. Med. 7, 1189–1193 (2001).
Kowal, C. et al. Cognition and immunity: antibody impairs memory. Immunity 21, 179–188 (2004).
Lauvsnes, M. B. & Omdal, R. Systemic lupus erythematosus, the brain, and anti-NR2 antibodies. J. Neurol. 259, 622–629 (2012).
Yoshio, T., Onda, K., Nara, H. & Minota, S. Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 54, 675–678 (2006).
Arinuma, Y., Yanagida, T. & Hirohata, S. Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 58, 1130–1135 (2008).
Bonfa, E. et al. Association between lupus psychosis and anti-ribosomal P protein antibodies. N. Engl. J. Med 317, 265–271 (1987).
Briani, C. et al. Neurolupus is associated with anti-ribosomal P protein antibodies: an inception cohort study. J. Autoimmun. 32, 79–84 (2009).
Hirohata, S., Arinuma, Y., Takayama, M. & Yoshio, T. Association of cerebrospinal fluid anti-ribosomal P protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res. Ther. 9, R44 (2007).
Karassa, F. B. et al. Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Arthritis Rheum. 54, 312–324 (2006).
Teh, L. S. & Isenberg, D. A. Antiribosomal P protein antibodies in systemic lupus erythematosus. A reappraisal. Arthritis Rheum. 37, 307–315 (1994).
Hanly, J. G. et al. Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. Ann. Rheum. Dis. 70, 1726–1732 (2011).
Hanly, J. G. Antiphospholipid syndrome: an overview. CMAJ 168, 1675–1682 (2003).
Musial, J. Antiphospholipid antibodies and thrombosis. Thromb. Res. 129, 345–347 (2012).
Love, P. E. & Santoro, S. A. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann. Intern. Med. 112, 682–698 (1990).
Menon, S. et al. A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum. 42, 735–741 (1999).
Hanly, J. G., Hong, C., Smith, S. & Fisk, J. D. A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum. 42, 728–734 (1999).
Chapman, J., Cohen-Armon, M., Shoenfeld, Y. & Korczyn, A. D. Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes. Lupus 8, 127–133 (1999).
Hirohata, S. & Miyamoto, T. Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum. 33, 644–649 (1990).
Shiozawa, S., Kuroki, Y., Kim, M., Hirohata, S. & Ogino, T. Interferon-α in lupus psychosis. Arthritis Rheum. 35, 417–422 (1992).
Jara, L. J. et al. Prolactin and interleukin-6 in neuropsychiatric lupus erythematosus. Clin. Rheumatol. 17, 110–114 (1998).
Hirohata, S. & Hayakawa, K. Enhanced interleukin-6 messenger RNA expression by neuronal cells in a patient with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 42, 2729–2730 (1999).
Trysberg, E., Carlsten, H. & Tarkowski, A. Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus 9, 498–503 (2000).
Rood, M. J. et al. Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes. Ann. Rheum. Dis. 58, 85–89 (1999).
Gilad, R., Lampl, Y., Eshel, Y., Barak, V. & Sarova-Pinhas, I. Cerebrospinal fluid soluble interleukin-2 receptor in cerebral lupus. Br. J. Rheumatol. 36, 190–193 (1997).
Santer, D. M., Yoshio, T., Minota, S., Moller, T. & Elkon, K. B. Potent induction of IFN-α and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus. J. Immunol. 182, 1192–1201 (2009).
Sato, S., Kawashima, H., Hoshika, A. & Yoshio, T. Clinical analysis of anti-NR2 glutamate receptor antibodies and interleukin-6 with neuropsychiatric systemic lupus erythematosus. Rheumatology (Oxford) 50, 2142–2144 (2011).
Hanly, J. G. New insights into central nervous system lupus: a clinical perspective. Curr. Rheumatol. Rep. 9, 116–124 (2007).
Bertsias, G. K. et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann. Rheum. Dis. 69, 2074–2082 (2010).
Esdaile, J. M. et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 44, 2331–2337 (2001).
Urowitz, M. B. et al. Atherosclerotic vascular events in a multinational inception cohort of systemic lupus erythematosus. Arthritis Care Res. (Hoboken) 62, 881–887 (2010).
Govoni, M. et al. Factors and comorbidities associated with first neuropsychiatric event in systemic lupus erythematosus: does a risk profile exist? A large multicentre retrospective cross-sectional study on 959 Italian patients. Rheumatology (Oxford) 51, 157–168 (2012).
Florica, B. et al. Peripheral neuropathy in patients with systemic lupus erythematosus. Semin. Arthritis Rheum. 41, 203–211 (2011).
Toledano, P., Sarbu, N., Espinosa, G., Bargallo, N. & Cervera, R. Neuropsychiatric systemic lupus erythematosus: magnetic resonance imaging findings and correlation with clinical and immunological features. Autoimmun. Rev. 12, 1166–1170 (2013).
Jarpa, E. et al. Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity. Lupus 20, 58–66 (2011).
Shimojima, Y., Matsuda, M., Gono, T., Ishii, W. & Ikeda, S. Relationship between clinical factors and neuropsychiatric manifestations in systemic lupus erythematosus. Clin. Rheumatol. 24, 469–475 (2005).
Omdal, R. et al. Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur. J. Neurol. 12, 392–398 (2005).
Lapteva, L. et al. Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum. 54, 2505–2514 (2006).
Hanly, J. G., Robichaud, J. & Fisk, J. D. Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus. J. Rheumatol. 33, 1553–1558 (2006).
Harrison, M. J., Ravdin, L. D. & Lockshin, M. D. Relationship between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus. Arthritis Rheum. 54, 2515–2522 (2006).
Steup-Beekman, G., Steens, S., van Buchem, M. & Huizinga, T. Anti-NMDA receptor autoantibodies in patients with systemic lupus erythematosus and their first-degree relatives. Lupus 16, 329–334 (2007).
Birnbaum, J. & Kerr, D. Devic's syndrome in a woman with systemic lupus erythematosus: diagnostic and therapeutic implications of testing for the neuromyelitis optica IgG autoantibody. Arthritis Rheum. 57, 347–351 (2007).
Waters, P. et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch. Neurol. 65, 913–919 (2008).
Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S. & Hinson, S. R. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J. Exp. Med. 202, 473–477 (2005).
Vieira-Karuta, S. C. et al. Epileptic seizures and EEG features in juvenile systemic lupus erythematosus. Arq. Neuropsiquiatr. 66, 468–470 (2008).
Alarcon, G. S. et al. Systemic lupus erythematosus in three ethnic groups. X. Measuring cognitive impairment with the cognitive symptoms inventory. Arthritis Rheum. 47, 310–319 (2002).
Julian, L. J. et al. Validity of brief screening tools for cognitive impairment in rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res. (Hoboken) 64, 448–454 (2012).
Hanly, J. G., Omisade, A., Su, L., Farewell, V. & Fisk, J. D. Assessment of cognitive function in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis by computerized neuropsychological tests. Arthritis Rheum. 62, 1478–1486 (2010).
Sibbitt, W. L., Jr, Sibbitt, R. R. & Brooks, W. M. Neuroimaging in neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 42, 2026–2038 (1999).
Peterson, P. L., Howe, F. A., Clark, C. A. & Axford, J. S. Quantitative magnetic resonance imaging in neuropsychiatric systemic lupus erythematosus. Lupus 12, 897–902 (2003).
Appenzeller, S., Pike, G. B. & Clarke, A. E. Magnetic resonance imaging in the evaluation of central nervous system manifestations in systemic lupus erythematosus. Clin. Rev. Allergy Immunol. 34, 361–366 (2008).
Rovaris, M. et al. Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J. Neurol. Neurosurg. Psychiatry 68, 170–177 (2000).
Graham, J. W. & Jan, W. MRI and the brain in systemic lupus erythematosus. Lupus 12, 891–896 (2003).
Hanly, J. G. Evaluation of patients with CNS involvement in SLE. Baillieres Clin. Rheumatol. 12, 415–431 (1998).
Nossent, J. C., Hovestadt, A., Schonfeld, D. H. & Swaak, A. J. Single-photon-emission computed tomography of the brain in the evaluation of cerebral lupus. Arthritis Rheum. 34, 1397–1403 (1991).
Oku, K. et al. Cerebral imaging by magnetic resonance imaging and single photon emission computed tomography in systemic lupus erythematosus with central nervous system involvement. Rheumatology (Oxford) 42, 773–777 (2003).
Rubbert, A. et al. Single-photon-emission computed tomography analysis of cerebral blood flow in the evaluation of central nervous system involvement in patients with systemic lupus erythematosus. Arthritis Rheum. 36, 1253–1262 (1993).
Rogers, M. P. et al. I-123 iofetamine SPECT scan in systemic lupus erythematosus patients with cognitive and other minor neuropsychiatric symptoms: a pilot study. Lupus 1, 215–219 (1992).
Kovacs, J. A., Urowitz, M. B., Gladman, D. D. & Zeman, R. The use of single photon emission computerized tomography in neuropsychiatric SLE: a pilot study. J. Rheumatol. 22, 1247–1253 (1995).
Waterloo, K. et al. Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow. J. Neurol. 248, 595–602 (2001).
Fitzgibbon, B. M. et al. Functional MRI in NPSLE patients reveals increased parietal and frontal brain activation during a working memory task compared with controls. Rheumatology (Oxford) 47, 50–53 (2008).
DiFrancesco, M. W. et al. Functional magnetic resonance imaging assessment of cognitive function in childhood-onset systemic lupus erythematosus: a pilot study. Arthritis Rheum. 56, 4151–4163 (2007).
Barile-Fabris, L. et al. Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann. Rheum. Dis. 64, 620–625 (2005).
Fernandez, M., Trevisani, V. F., Castro, A. A., Neves Neto, J. F. & Atallah, A. N. Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD002265. http://dx.doi.org/10.1002/14651858.CD002265.pub3.
Mok, C. C., Lau, C. S. & Wong, R. W. Treatment of lupus psychosis with oral cyclophosphamide followed by azathioprine maintenance: an open-label study. Am. J. Med. 115, 59–62 (2003).
Tokunaga, M. et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann. Rheum. Dis. 66, 470–475 (2007).
Finazzi, G. et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS). J. Thromb. Haemost. 3, 848–853 (2005).
Crowther, M. A. et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N. Engl. J. Med. 349, 1133–1138 (2003).
Ruiz-Irastorza, G., Hunt, B. J. & Khamashta, M. A. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum. 57, 1487–1495 (2007).
Jung, H. et al. The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus. Arthritis Rheum. 62, 863–868 (2010).
Meroni, P. L. et al. Statins prevent endothelial cell activation induced by antiphospholipid (anti-β2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. Arthritis Rheum. 44, 2870–2878 (2001).
Denburg, S. D., Carbotte, R. M. & Denburg, J. A. Corticosteroids and neuropsychological functioning in patients with systemic lupus erythematosus. Arthritis Rheum. 37, 1311–1320 (1994).
Petri, M., Naqibuddin, M., Sampedro, M., Omdal, R. & Carson, K. A. Memantine in systemic lupus erythematosus: a randomized, double-blind placebo-controlled trial. Semin. Arthritis Rheum. 41, 194–202 (2011).
Harrison, M. J. et al. Results of intervention for lupus patients with self-perceived cognitive difficulties. Neurology 65, 1325–1327 (2005).
Karlson, E. W. et al. A randomized clinical trial of a psychoeducational intervention to improve outcomes in systemic lupus erythematosus. Arthritis Rheum. 50, 1832–1841 (2004).
McCune, W. J. et al. Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus. N. Engl. J. Med. 318, 1423–1431 (1988).
Hanly, J. G., Cassell, K. & Fisk, J. D. Cognitive function in systemic lupus erythematosus: results of a 5-year prospective study. Arthritis Rheum. 40, 1542–1543 (1997).
Waterloo, K., Omdal, R., Husby, G. & Mellgren, S. I. Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study. Rheumatology (Oxford) 41, 411–415 (2002).
Karassa, F. B. et al. Predictors of clinical outcome and radiologic progression in patients with neuropsychiatric manifestations of systemic lupus erythematosus. Am. J. Med. 109, 628–634 (2000).
Boers, M. Understanding the window of opportunity concept in early rheumatoid arthritis. Arthritis Rheum. 48, 1771–1774 (2003).
Cush, J. J. Early rheumatoid arthritis—is there a window of opportunity? J. Rheumatol. 80 (Suppl.), 1–7 (2007).
Acknowledgements
The author's work is supported by the Government of Canada, Canadian Institutes of Health Research grant number MOP 86526.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no competing financial interests.
Rights and permissions
About this article
Cite this article
Hanly, J. Diagnosis and management of neuropsychiatric SLE. Nat Rev Rheumatol 10, 338–347 (2014). https://doi.org/10.1038/nrrheum.2014.15
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrrheum.2014.15
This article is cited by
-
Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice
Journal of Neuroinflammation (2023)
-
Novel CSF biomarkers for diagnosis and integrated analysis of neuropsychiatric systemic lupus erythematosus: based on antibody profiling
Arthritis Research & Therapy (2023)
-
The influence of intrathecal injection of methotrexate and dexamethasone on neuropsychiatric systemic lupus erythematosus (NPSLE): a retrospective cohort study of 386 patients with NPSLE
Arthritis Research & Therapy (2023)
-
Neuropsychiatric lupus erythematosus with neurogenic pulmonary edema and anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor limbic encephalitis: a case report
BMC Neurology (2022)
-
Abnormal cortical thickness and structural covariance networks in systemic lupus erythematosus patients without major neuropsychiatric manifestations
Arthritis Research & Therapy (2022)