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Neuropsychiatric lupus

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Abstract

Neuropsychiatric (NP) manifestations of systemic lupus erythematosus (SLE) have been recognized for more than 100 years but continue to pose a diagnostic and therapeutic challenge for rheumatologists and other physicians involved in the care of SLE patients. NP-SLE includes a plethora of clinical manifestations and the reported prevalence has varied widely between 14% and 75%. The recent introduction of a standard nomenclature, case definitions, and diagnostic criteria for19 NP-SLE syndromes should facilitate a more consistent approach to the classification of patients and to the execution of large multicenter clinical studies. The etiology of NP-SLE is likely multifactorial and includes microangiopathy, autoantibody production, and the intrathecal production of proinflammatory cytokines. Newer imaging modalities of brain structure and function provide novel ways of understanding pathogenic mechanisms. The use of standardized neuropsychometric techniques to evaluate cognitive function has identified a high prevalence of cognitive impairment in SLE patients. The management of patients with NP-SLE includes symptomatic and immunosuppressive therapies, evidence for which is largely limited to uncontrolled clinical trials and anecdotal experience. Multicenter initiatives are required to address important issues on prognosis and management.

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References and Recommended Reading

  1. Osler W: On the visceral complications of erythema exudativum multiforme. Am J Med Sci 1895, 110:629–646.

    Article  Google Scholar 

  2. American College of Rheumatology: The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999, 42:599–608. A standard nomenclature and set of case definitions for 19 neuropsychiatric syndromes in patients with systemic lupus erythematosus has been developed by the ACR research committee. Guidelines for reporting standards and specific diagnostic tests are recommended for each syndrome. This provides a basis for a uniform classification of patients with NP-SLE.

    Article  Google Scholar 

  3. McCune WJ, Golbus J: Neuropsychiatric lupus. Rheum Dis Clin North Am 1988, 14:149–167.

    PubMed  CAS  Google Scholar 

  4. Hanly JG, Liang MH: Cognitive disorders in systemic lupus erythematosus. Epidemiologic and clinical issues. Ann N Y Acad Sci 1997, 823:60–68.

    Article  PubMed  CAS  Google Scholar 

  5. Sibley JT, Olszynski WP, Decoteau WE, Sundaram MB: The incidence and prognosis of central nervous system disease in systemic lupus erythematosus. J Rheumatol 1992, 19:47–52.

    PubMed  CAS  Google Scholar 

  6. Estes D, Christian CL: The natural history of systemic lupus erythematosus by prospective analysis. Medicine (Baltimore) 1971, 50:85–95.

    CAS  Google Scholar 

  7. Ginzler EM, Diamond HS, Weiner M, et al.: A multicenter study of outcome in systemic lupus erythematosus, I: Entry variables as predictors of prognosis. Arthritis Rheum 1982, 25:601–611.

    Article  PubMed  CAS  Google Scholar 

  8. Lee P, Urowitz MB, Bookman AA, 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 1977, 46:1–32.

    PubMed  CAS  Google Scholar 

  9. Feinglass EJ, Arnett FC, Dorsch CA, Zizic TM, Stevens MB: Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine (Baltimore) 1976, 55:323–339.

    Article  CAS  Google Scholar 

  10. Kovacs JA, Urowitz MB, Gladman DD: Dilemmas in neuropsychiatric lupus. Rheum Dis Clin North Am 1993, 19:795–814.

    PubMed  CAS  Google Scholar 

  11. Hanly JG, Cassell K, Fisk JD: Cognitive function in systemic lupus erythematosus: results of a 5-year prospective study. Arthritis Rheum 1997, 40:1542–1543. The change in cognitive performance, determined by sequential neuropsychological assessments, in an unselected group of SLE patients is described. In general the abnormalities in cognitive performance were mild and evanescent. Unless accompanied by clinically overt neuropsychiatric disease, the detection of cognitive impairment did not predict subsequent deterioration in cognitive performance over 5 years.

    Article  PubMed  CAS  Google Scholar 

  12. 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, 53:298–303.

    PubMed  CAS  Google Scholar 

  13. Gladman DD, Urowitz MB, Slonim D, et al.: Evaluation of predictive factors for neurocognitive dysfunction in patients with inactive systemic lupus erythematosus. J Rheumatol 2000, 27:2367–2371.

    PubMed  CAS  Google Scholar 

  14. Johnson RT, Richardson EP: The neurological manifestations of systemic lupus erythematosus. Medicine (Baltimore) 1968, 47:337–369.

    Article  CAS  Google Scholar 

  15. Hanly JG, Walsh NM, Sangalang V: Brain pathology in systemic lupus erythematosus. J Rheumatol 1992, 19:732–741.

    PubMed  CAS  Google Scholar 

  16. Weiner SM, Klein R, Berg PA: A longitudinal study of autoantibodies against central nervous system tissue and gangliosides in connective tissue diseases. Rheumatol Int 2000, 19:83–88.

    Article  PubMed  CAS  Google Scholar 

  17. Bluestein HG, Williams GW, Steinberg AD: Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus. Am J Med 1981, 70:240–246.

    Article  PubMed  CAS  Google Scholar 

  18. Zvaifler NJ, Bluestein HG: The pathogenesis of central nervous system manifestations of systemic lupus erythematosus. Arthritis Rheum 1982, 25:862–866.

    Article  PubMed  CAS  Google Scholar 

  19. Martinez-Cordero E, Rivera Garcia BE, Aguilar Leon DE: Anticardiolipin antibodies in serum and cerebrospinal fluid from patients with systemic lupus erythematosus. J Invest Allergol Clin Immunol 1997, 7:596–601.ba]

    CAS  Google Scholar 

  20. Karpiak SE, Graf L, Rapport MM: Antiserum to brain gangliosides produces recurrent epileptiform activity. Science 1976, 194:735–737.

    Article  PubMed  CAS  Google Scholar 

  21. Kobiler D, Fuchs S, Samuel D: The effect of antisynaptosomal plasma membrane antibodies on memory. Brain Res 1976, 115:129–138.

    Article  PubMed  CAS  Google Scholar 

  22. Gaburo NJ, Timo-laria C, Bueno C, et al.: ‘In vivo’ effects of anti-ribosomal P protein antibodies injections into lateral of the rat brain [abstract 864]. Arthritis Rheum 1995:38.

  23. Hanson VG, Horowitz M, Rosenbluth D, Spiera H, Puszkin S: Systemic lupus erythematosus patients with central nervous system involvement show autoantibodies to a 50-kD neuronal membrane protein. J Exp Med 1992, 176:565–573.

    Article  PubMed  CAS  Google Scholar 

  24. Galeazzi M, Annunziata P, Sebastiani GD, et al.: Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE. J Rheumatol 2000, 27:135–141.

    PubMed  CAS  Google Scholar 

  25. Martinez X, Tintore M, Montalban J, et al.: Antibodies against gangliosides in patients with SLE and neurological manifestations. Lupus 1992, 1:299–302.

    PubMed  CAS  Google Scholar 

  26. Pereira RM, Yoshinari NH, De Oliveira RM, Cossermelli W: Antiganglioside antibodies in patients with neuropsychiatric systemic lupus erythematosus. Lupus 1992, 1:175–179.

    PubMed  CAS  Google Scholar 

  27. Teh LS, Isenberg DA: Antiribosomal P protein antibodies in systemic lupus erythematosus. A reappraisal. Arthritis Rheum 1994, 37:307–315.

    Article  PubMed  CAS  Google Scholar 

  28. Bonfa E, Golombek SJ, Kaufman LD, et al.: Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med 1987, 317:265–271.

    Article  PubMed  CAS  Google Scholar 

  29. Arnett FC, Reveille JD, Moutsopoulos HM, Georgescu L, Elkon KB: Ribosomal P autoantibodies in systemic lupus erythematosus. Frequencies in different ethnic groups and clinical and immunogenetic associations. Arthritis Rheum 1996, 39:1833–1839.In this study of 394 patients with SLE, 63 of whom had anti-P antibodies, the authors report a significant association with psychosis and depression with odds ratios between 4 and 10. The presence of anti-P antibodies was strongly influenced by certain MHC class II alleles.

    Article  PubMed  CAS  Google Scholar 

  30. Koren E, Reichlin MW, Koscec M, Fugate RD, Reichlin M: Autoantibodies to the ribosomal P proteins react with a plasma membrane-related target on human cells. J Clin Invest 1992, 89:1236–1241.

    Article  PubMed  CAS  Google Scholar 

  31. Isshi K, Hirohata S: Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus. Arthritis Rheum 1998, 41:1819–1827. The authors report a significant elevation in circulating anti-P antibodies in 34 patients with lupus psychosis, but there was no elevation in the level of serum antineuronal antibodies. In contrast, examination of the CSF from the same patients revealed a significant elevation in antineuronal antibodies but not in anti-P antibody levels.

    Article  PubMed  CAS  Google Scholar 

  32. Love PE, Santoro SA: Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann Intern Med 1990, 112:682–698.

    PubMed  CAS  Google Scholar 

  33. Petri M: Pathogenesis and treatment of the antiphospholipid antibody syndrome. Med Clin North Am 1997, 81:151–177.

    Article  PubMed  CAS  Google Scholar 

  34. Hanly JG, Hong C, Smith S, Fisk JD: A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum 1999, 42:728–734. In a 5-year prospective study of 51 patients with SLE, the authors report an association between the presence of persistently elevated anticardiolipin antibodies with deterioration in specific subsets of cognitive function.

    Article  PubMed  CAS  Google Scholar 

  35. 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, 42:735–741. A 2-year prospective study of 45 patients with SLE indicated a deterioration in selected aspects of cognitive function in those patients with persistent elevation in IgG anticardiolipin antibodies.

    Article  PubMed  CAS  Google Scholar 

  36. Chapman J, Cohen-Armon M, Shoenfeld Y, Korczyn AD: Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes. Lupus 1999, 8:127–133.

    Article  PubMed  CAS  Google Scholar 

  37. 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 1990, 33:644–649.

    Article  PubMed  CAS  Google Scholar 

  38. Shiozawa S, Kuroki Y, Kim M, Hirohata S, Ogino T: Interferonalpha in lupus psychosis. Arthritis Rheum 1992, 35:417–422.

    Article  PubMed  CAS  Google Scholar 

  39. Jara LJ, Irigoyen L, Ortiz MJ, et al.: Prolactin and interleukin-6 in neuropsychiatric lupus erythematosus. Clin Rheumatol 1998, 17:110–114.

    Article  PubMed  CAS  Google Scholar 

  40. Hirohata S, Hayakawa K: Enhanced interleukin-6 messenger RNA expression by neuronal cells in a patient with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 1999, 42:2729–2730.

    Article  PubMed  CAS  Google Scholar 

  41. Trysberg E, Carlsten H, Tarkowski A: Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus 2000, 9:498–503. The authors have measured the levels of a variety of cytokines in serum and CSF of patients with SLE and report a significant elevation in CSF IL-6 and IL-8 levels in patients with NP-SLE. No association with any particular clinical subset of NP-SLE was reported.

    Article  PubMed  CAS  Google Scholar 

  42. Rood MJ, Keijsers V, van der Linden MW, et al.: Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes. Ann Rheum Dis 1999, 58:85–89.

    Article  PubMed  CAS  Google Scholar 

  43. Gilad R, Lampl Y, Eshel Y, Barak V, Sarova-Pinhas I: Cerebrospinal fluid soluble interleukin-2 receptor in cerebral lupus. Br J Rheumatol 1997, 36:190–193.

    Article  PubMed  CAS  Google Scholar 

  44. Sibbitt WL Jr, Sibbitt RR, Brooks WM: Neuroimaging in neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 1999, 42:2026–2038.This is an excellent review of the potential for neuroimaging in patients with NP-SLE, written by authors with considerable experience and expertise in the area.

    Article  PubMed  Google Scholar 

  45. Bell CL, Partington C, Robbins M, et al.: Magnetic resonance imaging of central nervous system lesions in patients with lupus erythematosus. Correlation with clinical remission and antineurofilament and anticardiolipin antibody titers. Arthritis Rheum 1991, 34:432–441.

    Article  PubMed  CAS  Google Scholar 

  46. Hanly JG: Evaluation of patients with CNS involvement in SLE. Baillieres Clin Rheumatol 1998, 12:415–431.

    Article  PubMed  CAS  Google Scholar 

  47. Hanly JG: Single photon emission computed tomography scanning in neuropsychiatric systemic lupus erythematosus. J Rheumatol 1998, 25:401–403.

    PubMed  CAS  Google Scholar 

  48. Kao CH, Ho YJ, Lan JL, et al.: Discrepancy between regional cerebral blood flow and glucose metabolism of the brain in systemic lupus erythematosus patients with normal brain magnetic resonance imaging findings. Arthritis Rheum 1999, 42:61–68.

    Article  PubMed  CAS  Google Scholar 

  49. Otte A, Weiner SM, Hoegerle S, et al.: Neuropsychiatric systemic lupus erythematosus before and after immunosuppressive treatment: a FDG PET study. Lupus 1998, 7:57–59.

    Article  PubMed  CAS  Google Scholar 

  50. Weiner SM, Otte A, Schumacher M, et al.: Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus. Lupus 2000, 9:386–389.

    Article  PubMed  CAS  Google Scholar 

  51. Brooks WM, Jung RE, Ford CC, Greinel EJ, Sibbitt WL Jr: Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus. J Rheumatol 1999, 26:81–85.

    PubMed  CAS  Google Scholar 

  52. Sabet A, Sibbitt WL Jr, Stidley CA, Danska J, Brooks WM: Neurometabolite markers of cerebral injury in the antiphospholipid antibody syndrome of systemic lupus erythematosus. Stroke 1998, 29:2254–2260.

    PubMed  CAS  Google Scholar 

  53. Bosma GP, Rood MJ, Zwinderman AH, Huizinga TW, van Buchem MA: Evidence of central nervous system damage in patients with neuropsychiatric systemic lupus erythematosus, demonstrated by magnetization transfer imaging. Arthritis Rheum 2000, 43:48–54.

    Article  PubMed  CAS  Google Scholar 

  54. Denburg SD, Carbotte RM, Denburg JA: Corticosteroids and neuropsychological functioning in patients with systemic lupus erythematosus. Arthritis Rheum 1994, 37:1311–1320.

    Article  PubMed  CAS  Google Scholar 

  55. Trevisani VF, Castro AA, Neves Neto JF, Atallah AN: Cyclophosphamide versus methylprednisolone for the treatment of neuropsychiatric involvement in systemic lupus erythematosus (Cochrane review). Cochrane Database Syst Rev 2000:3.

  56. Baca V, Lavalle C, Garcia R, et al.: Favorable response to intravenous methylprednisolone and cyclophosphamide in children with severe neuropsychiatric lupus. J Rheumatol 1999, 26:432–439.

    PubMed  CAS  Google Scholar 

  57. Khamashta MA, Cuadrado MJ, Mujic F, et al.: The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995, 332:993–997.

    Article  PubMed  CAS  Google Scholar 

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Hanly, J.G. Neuropsychiatric lupus. Curr Rheumatol Rep 3, 205–212 (2001). https://doi.org/10.1007/s11926-001-0020-7

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