Neuropsychiatric manifestations of systemic lupus erythematosus
- Peter H Schur, MD
Peter H Schur, MD
- Editor-in-Chief — Rheumatology
- Section Editor — Basic Science
- Professor of Medicine
- Harvard Medical School
- Section Editors
- Michael J Aminoff, MD, DSc
Michael J Aminoff, MD, DSc
- Editor-in-Chief — Neurology
- Section Editor — Medical Neurology
- Professor of Neurology
- University of California, San Francisco School of Medicine
- Jonathan M Silver, MD
Jonathan M Silver, MD
- Section Editor — Mental and Medical Disorders
- Clinical Professor of Psychiatry
- New York University School of Medicine
Central nervous system neuropsychiatric lupus refers to the various psychiatric and neurologic manifestations that develop secondary to involvement of the CNS in patients with systemic lupus erythematosus (SLE). These clinical features are characterized by some investigators as either diffuse (eg, encephalopathy, coma, depression, and psychosis) or complex (eg, encephalopathy with stroke or seizure, and psychiatric presentation with stroke or seizure) . Disturbances of mental function are the most common symptom.
Because of the varied diagnostic criteria associated with these manifestations, the American College of Rheumatology (ACR) has formulated case definitions, reporting standards, and diagnostic testing recommendations for the 19 neuropsychiatric SLE syndromes (table 1) . The full definitions can be found at the following Internet address: www.rheumatology.org/publications/ar/1999/aprilappendix.asp.
A psychiatric disturbance due to CNS lupus is a diagnosis of exclusion; all other possible causes of the observed symptoms must therefore be considered, including infection, electrolyte abnormalities, renal failure, drug effects, mass lesions, arterial emboli, and primary psychiatric disorders (such as bipolar disorder or severe stress disorder resulting from a chronic and life-threatening disease) . One clue to the diagnosis is that most acute psychiatric episodes occur during the first two years after the onset of SLE [4,5].
The term lupus cerebritis refers to the neuropsychiatric manifestations of lupus that appear to have an organic basis, rather than a specific pathophysiologic mechanism. The distinction between organic and functional causes of some neuropsychiatric symptoms can occasionally be made by assaying for specific autoantibodies.
●Some investigators believe that a strong association exists between the occurrence of neuropsychiatric symptoms and the presence of antineuronal antibodies and other antibodies [6-9].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- West SG, Emlen W, Wener MH, Kotzin BL. Neuropsychiatric lupus erythematosus: a 10-year prospective study on the value of diagnostic tests. Am J Med 1995; 99:153.
- The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42:599.
- Miguel EC, Pereira RM, Pereira CA, et al. Psychiatric manifestations of systemic lupus erythematosus: clinical features, symptoms, and signs of central nervous system activity in 43 patients. Medicine (Baltimore) 1994; 73:224.
- Sibley JT, Olszynski WP, Decoteau WE, Sundaram MB. The incidence and prognosis of central nervous system disease in systemic lupus erythematosus. J Rheumatol 1992; 19:47.
- Ward MM, Studenski S. The time course of acute psychiatric episodes in systemic lupus erythematosus. J Rheumatol 1991; 18:535.
- Hanly JG, Fisk JD, Eastwood B. Brain reactive autoantibodies and cognitive impairment in systemic lupus erythematosus. Lupus 1994; 3:193.
- Denburg SD, Behmann SA, Carbotte RM, Denburg JA. Lymphocyte antigens in neuropsychiatric systemic lupus erythematosus. Relationship of lymphocyte antibody specificities to clinical disease. Arthritis Rheum 1994; 37:369.
- Denburg JA, Behmann SA. Lymphocyte and neuronal antigens in neuropsychiatric lupus: presence of an elutable, immunoprecipitable lymphocyte/neuronal 52 kd reactivity. Ann Rheum Dis 1994; 53:304.
- Conti F, Alessandri C, Bompane D, et al. Autoantibody profile in systemic lupus erythematosus with psychiatric manifestations: a role for anti-endothelial-cell antibodies. Arthritis Res Ther 2004; 6:R366.
- Bonfa E, Golombek SJ, Kaufman LD, et al. Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med 1987; 317:265.
- Isshi K, Hirohata S. Association of anti-ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 1996; 39:1483.
- Gerli R, Caponi L, Tincani A, et al. Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: prospective evaluation in a large cohort of Italian patients. Rheumatology (Oxford) 2002; 41:1357.
- Carbotte RM, Denburg SD, Denburg JA. Cognitive deficit associated with rheumatic diseases: neuropsychological perspectives. Arthritis Rheum 1995; 38:1363.
- Hanly JG, Hong C, Smith S, Fisk JD. A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum 1999; 42:728.
- Omdal R, Brokstad K, Waterloo K, et al. Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol 2005; 12:392.
- Lapteva L, Nowak M, Yarboro CH, et al. Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum 2006; 54:2505.
- Harrison MJ, Ravdin LD, Lockshin MD. Relationship between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus. Arthritis Rheum 2006; 54:2515.
- Hanly JG. ACR classification criteria for systemic lupus erythematosus: limitations and revisions to neuropsychiatric variables. Lupus 2004; 13:861.
- Rogers MP. Psychiatric Aspects. In: The Clinical Management of Systemic Lupus Erythematosus, 2nd ed, Schur PH (Ed), Lippincott, Philadelphia 1996.
- Perry SW. Psychiatric aspects of systemic lupus erythematosus. In: Systemic Lupus Erythematosus, Lahita RG (Ed), John Wiley and Sons, New York 1987.
- Bluestein HG, Williams GW, Steinberg AD. Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus. Am J Med 1981; 70:240.
- Bhangle SD, Kramer N, Rosenstein ED. Corticosteroid-induced neuropsychiatric disorders: review and contrast with neuropsychiatric lupus. Rheumatol Int 2013; 33:1923.
- Schroeder JO, Euler HH, Löffler H. Synchronization of plasmapheresis and pulse cyclophosphamide in severe systemic lupus erythematosus. Ann Intern Med 1987; 107:344.
- Neuwelt CM, Lacks S, Kaye BR, et al. Role of intravenous cyclophosphamide in the treatment of severe neuropsychiatric systemic lupus erythematosus. Am J Med 1995; 98:32.
- Boumpas DT, Yamada H, Patronas NJ, et al. Pulse cyclophosphamide for severe neuropsychiatric lupus. Q J Med 1991; 81:975.
- Mok CC, Lau CS, Wong RW. Treatment of lupus psychosis with oral cyclophosphamide followed by azathioprine maintenance: an open-label study. Am J Med 2003; 115:59.
- Rogers, MP, Liang, MH, Waterhouse, E, et al. Disturbed cognition and systemic lupus erythematosus: A subset of central nervous system lupus. Submitted for publication.
- Hay EM. Psychiatric disorder and cognitive impairment in SLE. Lupus 1994; 3:145.
- Hanly JG, Fisk JD, Sherwood G, Eastwood B. Clinical course of cognitive dysfunction in systemic lupus erythematosus. J Rheumatol 1994; 21:1825.
- Ainiala H, Loukkola J, Peltola J, et al. The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 2001; 57:496.
- Kozora E, Ellison MC, West S. Depression, fatigue, and pain in systemic lupus erythematosus (SLE): relationship to the American College of Rheumatology SLE neuropsychological battery. Arthritis Rheum 2006; 55:628.
- Kozora E, Hanly JG, Lapteva L, Filley CM. Cognitive dysfunction in systemic lupus erythematosus: past, present, and future. Arthritis Rheum 2008; 58:3286.
- Menon S, Jameson-Shortall E, Newman SP, et al. A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum 1999; 42:735.
- McLaurin EY, Holliday SL, Williams P, Brey RL. Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology 2005; 64:297.
- Tektonidou MG, Varsou N, Kotoulas G, et al. Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging findings. Arch Intern Med 2006; 166:2278.
- Kozora E, Thompson LL, West SG, Kotzin BL. Analysis of cognitive and psychological deficits in systemic lupus erythematosus patients without overt central nervous system disease. Arthritis Rheum 1996; 39:2035.
- Hay EM, Black D, Huddy A, et al. Psychiatric disorder and cognitive impairment in systemic lupus erythematosus. Arthritis Rheum 1992; 35:411.
- Hanly JG, Fisk JD, Sherwood G, et al. Cognitive impairment in patients with systemic lupus erythematosus. J Rheumatol 1992; 19:562.
- Carbotte RM, Denburg SD, Denburg JA. Prevalence of cognitive impairment in systemic lupus erythematosus. J Nerv Ment Dis 1986; 174:357.
- Hay EM, Huddy A, Black D, et al. A prospective study of psychiatric disorder and cognitive function in systemic lupus erythematosus. Ann Rheum Dis 1994; 53:298.
- Fisk JD, Eastwood B, Sherwood G, Hanly JG. Patterns of cognitive impairment in patients with systemic lupus erythematosus. Br J Rheumatol 1993; 32:458.
- Oroszi G, Lapteva L, Davis E, et al. The Met66 allele of the functional Val66Met polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in systemic lupus erythematosus. Ann Rheum Dis 2006; 65:1330.
- Denburg SD, Carbotte RM, Denburg JA. Corticosteroids and neuropsychological functioning in patients with systemic lupus erythematosus. Arthritis Rheum 1994; 37:1311.
- Harrison MJ, Morris KA, Horton R, et al. Results of intervention for lupus patients with self-perceived cognitive difficulties. Neurology 2005; 65:1325.
- Ad Hoc Committee on Lupus Response Criteria: Cognition Sub-committee, Mikdashi JA, Esdaile JM, et al. Proposed response criteria for neurocognitive impairment in systemic lupus erythematosus clinical trials. Lupus 2007; 16:418.
- West SG. Neuropsychiatric lupus. Rheum Dis Clin North Am 1994; 20:129.
- Asherson RA, Mercey D, Phillips G, et al. Recurrent stroke and multi-infarct dementia in systemic lupus erythematosus: association with antiphospholipid antibodies. Ann Rheum Dis 1987; 46:605.
- Hoppmann RA, Peden JG, Ober SK. Central nervous system side effects of nonsteroidal anti-inflammatory drugs. Aseptic meningitis, psychosis, and cognitive dysfunction. Arch Intern Med 1991; 151:1309.
- Jennekens FG, Kater L. The central nervous system in systemic lupus erythematosus. Part 1. Clinical syndromes: a literature investigation. Rheumatology (Oxford) 2002; 41:605.
- Líndal E, Thorlacius S, Steinsson K, Stefánsson JG. Psychiatric disorders among subjects with systemic lupus erythematosus in an unselected population. Scand J Rheumatol 1995; 24:346.
- Goodwin JM, Goodwin JS, Kellner R. Psychiatric symptoms in disliked medical patients. JAMA 1979; 241:1117.
- Kozora E, Ellison MC, Waxmonsky JA, et al. Major life stress, coping styles, and social support in relation to psychological distress in patients with systemic lupus erythematosus. Lupus 2005; 14:363.
- Jump RL, Robinson ME, Armstrong AE, et al. Fatigue in systemic lupus erythematosus: contributions of disease activity, pain, depression, and perceived social support. J Rheumatol 2005; 32:1699.
- Shortall E, Isenberg D, Newman SP. Factors associated with mood and mood disorders in SLE. Lupus 1995; 4:272.
- Schneebaum AB, Singleton JD, West SG, et al. Association of psychiatric manifestations with antibodies to ribosomal P proteins in systemic lupus erythematosus. Am J Med 1991; 90:54.
- Utset TO, Golden M, Siberry G, et al. Depressive symptoms in patients with systemic lupus erythematosus: association with central nervous system lupus and Sjögren's syndrome. J Rheumatol 1994; 21:2039.
- McKinley PS, Ouellette SC, Winkel GH. The contributions of disease activity, sleep patterns, and depression to fatigue in systemic lupus erythematosus. A proposed model. Arthritis Rheum 1995; 38:826.
- Krupp LB, LaRocca NG, Muir J, Steinberg AD. A study of fatigue in systemic lupus erythematosus. J Rheumatol 1990; 17:1450.