Skip to main content
SpringerLink
Log in

Neuropsychiatric Manifestations in Systemic Lupus Erythematosus

Epidemiology, Pathophysiology and Management

  • Therapy In Practice
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Systemic lupus erythematosus (SLE) is a relapsing-remitting autoimmune disease with CNS involvement occurring in up to 75% of patients. However, the frequency of neuropsychiatric manifestations in SLE studies varies widely, depending on the type of manifestations included and the method used for evaluation. CNS involvement may be considered primary if directly related to SLE activity in the CNS or secondary when related to treatment, infections, metabolic abnormalities or other systemic manifestations such as uraemia and hypertension. The pathogenesis of neuropsychiatric SLE is as yet unknown, though numerous autoantibodies and cytokines have been suggested as possible mediators. However, independent of the aetiology of the insult, the final common pathway in neuropsychiatric SLE is the involvement of the cerebral microvasculature.

The diagnosis of primary CNS involvement by SLE is often difficult, as both focal and diffuse manifestations may occur and there is no gold standard for diagnosis. A high index of clinical suspicion, in addition to laboratory and neuroimaging findings may support the diagnosis. Treatment is mostly empirical, although one randomized controlled trial has shown that cyclophosphamide in addition to methylprednisolone is superior to methylprednisolone alone in severe neuropsychiatric SLE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kozora E, Arciniegas DB, Filley CM, et al. Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data. Cogn Behav Neurol 2005; 18: 159–62

    PubMed  Google Scholar 

  2. West SG. Neuropsychiatric lupus. Rheum Dis Clin North Am 1994; 20: 129–58

    PubMed  CAS  Google Scholar 

  3. Hanly JG, Walsh NM, Sangalang V. Brain pathology in systemic lupus erythematosus. J Rheumatol 1992; 19: 732–41

    PubMed  CAS  Google Scholar 

  4. Johnson RT, Richardson EP. The neurological manifestations of systemic lupus erythematosus. Medicine (Baltimore) 1968; 47: 337–69

    CAS  Google Scholar 

  5. Hanly JG. Neuropsychiatric lupus. Rheum Dis Clin North Am 2005; 31: 273–98, vi

    PubMed  Google Scholar 

  6. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–7

    PubMed  CAS  Google Scholar 

  7. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42: 599–608

    Google Scholar 

  8. Ainiala H, Loukkola J, Peltola J, et al. The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 2001; 57: 496–500

    PubMed  CAS  Google Scholar 

  9. Brey RL. Neuropsychiatric lupus: clinical and imaging aspects. Bull NYU Hosp Jt Dis 2007; 5: 194–9

    Google Scholar 

  10. Hanly JG, Fisk JD, McCurdy G, et al. Neuropsychiatric syndromes in patients with systemic lupus erythematosus and rheumatoid arthritis. J Rheumatol 2005; 32: 1459–6

    PubMed  Google Scholar 

  11. Bertsias GK, Boumpas DT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol 2010; 6: 358–67

    PubMed  Google Scholar 

  12. Brey RL, Holliday SL, Saklad AR, et al. Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology 2002; 58: 1214–20

    PubMed  CAS  Google Scholar 

  13. Hanly JG, McCurdy G, Fougere L, et al. Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical significance. J Rheumatol 2004; 31: 2156–62

    PubMed  Google Scholar 

  14. Hanly JG, Urowitz MB, Sanchez-Guerrero J, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum 2007; 56: 265–73

    PubMed  CAS  Google Scholar 

  15. Sibbitt Jr WL, Brandt JR, Johnson CR, et al. The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus. J Rheumatol 2002; 29: 1536–42

    PubMed  Google Scholar 

  16. Harel L, Sandborg C, Lee T, et al. Neuropsychiatric manifestations in pediatric systemic lupus erythematosus and association with antiphospholipid antibodies. J Rheumatol 2006; 33: 1873–7

    PubMed  CAS  Google Scholar 

  17. Yu HH, Lee JH, Wang LC, et al. Neuropsychiatric manifestations in pediatric systemic lupus erythematosus: a 20-year study. Lupus 2006; 15: 651–7

    PubMed  CAS  Google Scholar 

  18. Kivity S, Tsarfaty G, Agmon-Levin N, et al. Abnormal olfactory function demonstrated by manganese-enhanced MRI in mice with experimental neuropsychiatric lupus. Ann N Y Acad Sci 2010; 1193: 70–7

    PubMed  Google Scholar 

  19. Maciaszczyk K, Durko T, Waszczykowska E, et al. Auditory function in patients with systemic lupus erythematosus. Auris Nasus Larynx 2011; 38: 26–32

    PubMed  Google Scholar 

  20. Mikdashi J, Handwerger B. Predictors of neuropsychiatric damage in systemic lupus erythematosus: data from the Maryland lupus cohort. Rheumatology (Oxford) 2004; 43: 1555–60

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Feinglass EJ, Arnett FC, Dorsch CA, et al. Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine (Baltimore) 1976; 55: 323–39

    CAS  Google Scholar 

  23. Jonsen A, Bengston AA, Nived O, et al. Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality. Rheumatology 2002; 41: 1308–12

    PubMed  CAS  Google Scholar 

  24. Panopalis P, Julian L, Yazdany J, et al. Impact of memory impairment on employment status in persons with systemic lupus erythematosus. Arthritis Rheum 2007; 57: 1453–60

    PubMed  Google Scholar 

  25. Baker K, Pope J. Employment and work disability in systemic lupus erythematosus: a systematic review. Rheumatology (Oxford) 2009; 48: 281–4

    Google Scholar 

  26. Appenzeller S, Cendes F, Costallat LT. Cognitive impairment and employment status in systemic lupus erythematosus: a prospective longitudinal study. Arthritis Rheum 2009; 61: 680–7

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  28. Hanly JG, Su L, Farewell V, et al. Prospective study of neuropsychiatric events in systemic lupus erythematosus. J Rheumatol 2009; 36: 1449–59

    PubMed  Google Scholar 

  29. Hanly JG, Urowitz MB, Jackson D, et al. SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus. Ann Rheum Dis 2011; 70: 961–7

    PubMed  CAS  Google Scholar 

  30. Bertsias GK, Ioannidis JP, Aringer M, 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 2010; 69: 2074–82

    PubMed  CAS  Google Scholar 

  31. Appenzeller S, Cendes F, Costallat LT. Epileptic seizures in systemic lupus erythematosus. Neurology 2004; 63: 1808–12

    PubMed  Google Scholar 

  32. Appenzeller S, Cendes F, Costallat LT. Acute psychosis in systemic lupus erythematosus. Rheumatol Int 2008; 28: 237–43

    PubMed  Google Scholar 

  33. Pego-Reigosa JM, Isenberg DA. Psychosis due to systemic lupus erythematosus: characteristics and long-term outcome of this rare manifestation of the disease. Rheumatology (Oxford) 2008; 47: 1498–502

    CAS  Google Scholar 

  34. Hanly JG, Harrison MJ. Management of neuropsychiatric lupus. Best Pract Res Clin Rheumatol 2005 Oct; 19 (5): 799–821

    PubMed  Google Scholar 

  35. Appenzeller S, Costallat LT. Clinical implications of migraine in systemic lupus erythematosus: relation to cumulative organ damage. Cephalalgia 2004; 24: 1024–30

    PubMed  CAS  Google Scholar 

  36. Davey R, Bamford J, Emery P. The ACR classification criteria for headache disorders in SLE fail to classify certain prevalent headache types. Cephalalgia 2008; 28: 296–9

    PubMed  CAS  Google Scholar 

  37. Ainiala H, Hietaharju A, Loukkola J, et al. Validity of the new American College of Rheumatology criteria for neuropsychiatric lupus syndromes: a population-based evaluation. Arthritis Rheum 2001; 45: 419–23

    PubMed  CAS  Google Scholar 

  38. Zhou HQ, Zhang FC, Tian XP, et al. Clinical features and outcome of neuropsychiatric lupus in Chinese: analysis of 240 hospitalized patients. Lupus 2008; 17: 93–9

    PubMed  CAS  Google Scholar 

  39. Muscal E, Brey RL. Neurologic manifestations of systemic lupus erythematosus in children and adults. Neurol Clin 2010; 28: 61–73

    PubMed  Google Scholar 

  40. Joseph FG, Scolding NJ. Neurolupus. Pract Neurol 2010; 10: 4–15

    PubMed  Google Scholar 

  41. Bessant R, Hingorani A, Patel L, et al. Risk of coronary heart disease and stroke in a large British cohort of patients with systemic lupus erythematosus. Rheumatology (Oxford) 2004; 43: 924–9

    CAS  Google Scholar 

  42. Seawell AH, Danoff-Burg S. Psychosocial research on systemic lupus erythematosus: a literature review. Lupus 2004; 13: 891–9

    PubMed  CAS  Google Scholar 

  43. Bachen EA, Chesney MA, Criswell LA. Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus. Arthritis Rheum 2009; 61: 822–9

    PubMed  Google Scholar 

  44. Appenzeller S, Veilleux M, Clarke A. Third cranial nerve palsy or pseudo 3rd nerve palsy of myasthenia gravis? A challenging diagnosis in systemic lupus erythematosus. Lupus 2009; 18: 836–40

    PubMed  CAS  Google Scholar 

  45. Carlomagno S, Migliaresi S, Ambrosone L, et al. Cognitive impairment in systemic lupus erythematosus: a follow-up study. J Neurol 2000; 247: 273–9

    PubMed  CAS  Google Scholar 

  46. Karassa FB, Ioannidis JP, Boki KA, et al. Predictors of clinical outcome and radiologic progression in patients with neuropsychiatric manifestations of systemic lupus erythematosus. Am J Med 2000; 109: 628–34

    PubMed  CAS  Google Scholar 

  47. Appenzeller S, Carnevalle AD, Li LM, et al. Hippocampal atrophy in systemic lupus erythematosus. Ann Rheum Dis 2006; 65: 1585–9

    PubMed  CAS  Google Scholar 

  48. Hanly JG, Fisk JD, Sherwood G, et al. Clinical course of cognitive dysfunction in systemic lupus erythematosus. J Rheumatol 1994; 2: 1825–31

    Google Scholar 

  49. 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 

  50. Waterloo K, Omdal R, Husby G, et al. Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study. Rheumatology (Oxford) 2002; 41: 411–5

    CAS  Google Scholar 

  51. Petri M, Naqibuddin M, Carson KA, et al. Brain magnetic resonance imaging in newly diagnosed systemic lupus erythematosus. J Rheumatol 2008; 35: 2348–54

    PubMed  Google Scholar 

  52. Devinsky O, Petito CK, Alonso DR. Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura. Ann Neurol 1988; 23: 380–4

    PubMed  CAS  Google Scholar 

  53. Ellis SG, Verity MA. Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955–1977. Sem Arthritis Rheum 1979; 8: 212–21

    CAS  Google Scholar 

  54. Zvaifler NJ, Bluestein HG. The pathogenesis of central nervous system manifestations of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 862–6

    PubMed  CAS  Google Scholar 

  55. Abbott NJ, Mendonca LL, Dolman DE. The blood-brain barrier in systemic lupus erythematosus. Lupus 2003; 12: 908–15

    PubMed  CAS  Google Scholar 

  56. Brooks WM, Sibbitt Jr WL, Kornfeld M, et al. The histopathologic associates of neurometabolite abnormalities in fatal neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 2010; 62: 2055–63

    PubMed  CAS  Google Scholar 

  57. Belmont HM, Abramson SB, Lie JT. Pathology and pathogenesis of vascular injury in systemic lupus erythematosus: interactions of inflammatory cells and activated endothelium. Arthritis Rheum 1996; 39: 9–22

    PubMed  CAS  Google Scholar 

  58. Appenzeller S, Amorim BJ, Ramos CD, et al. Voxel-based morphometry of brain SPECT can detect the presence of active central nervous system involvement in systemic lupus erythematosus. Rheumatology (Oxford) 2007; 46: 467–72

    CAS  Google Scholar 

  59. Appenzeller S, Li LM, Costallat LT, et al. Evidence of reversible axonal dysfunction in systemic lupus erythematosus: a proton MRS study. Brain 2005; 128: 2933–40

    PubMed  Google Scholar 

  60. Postal M, Appenzeller S. Central nervous system manifestations in systemic lupus erythematosus: diagnosis to treatment. In: Columbus F, editor. Autoimmune diseases: symptoms, diagnosis and treatment. New York (NY): Nova Science Publishers, Inc., 2001: 209–31

    Google Scholar 

  61. Karpiak SE, Graf L, Rapport MM. Antiserum to brain gangliosides produces recurrent epileptiform activity. Science 1976; 194: 735–7

    PubMed  CAS  Google Scholar 

  62. Zaccagni H, Fried J, Cornell J, et al. Soluble adhesion molecule levels, neuropsychiatric lupus and lupus-related damage. Front Biosci 2004; 9: 1654–9

    PubMed  CAS  Google Scholar 

  63. Matsuda J, Gohchi K, Gotoh M, et al. Circulating intercellular adhesion molecule-1 and soluble interleukin 2-receptor in patients with systemic lupus erythematosus. Eur J Haematol 1994; 52: 302–3

    PubMed  CAS  Google Scholar 

  64. Sfikakis PP, Charalambopoulos D, Vayiopoulos G, et al. Increased levels of intercellular adhesion molecule-1 in the serum of patients with systemic lupus erythematosus. Clin Exp Rheumatol 1994; 12: 5–9

    PubMed  CAS  Google Scholar 

  65. Spronk PE, Bootsma H, Huitema MG, et al. Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study. Clin Exp Rheumatol 1994; 97: 439–44

    CAS  Google Scholar 

  66. Trysberg E, Carlsten H, Tarkowski A. Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus 2000; 9: 498–503

    PubMed  CAS  Google Scholar 

  67. Shiozawa S, Kuroki Y, Kim M, et al. Interferon-alpha in lupus psychosis. Arthritis Rheum 1992; 35: 417–22

    PubMed  CAS  Google Scholar 

  68. Faber-Elmann A, Sthoeger Z, Tcherniack A, et al. Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus. Clin Exp Immunol 2002; 127: 393–8

    PubMed  CAS  Google Scholar 

  69. Ainiala H, Hietaharju A, Dastidar P, et al. Increased serum matrix metalloproteinase 9 levels in systemic lupus erythematosus patients with neuropsychiatric manifestations and brain magnetic resonance imaging abnormalities. Arthritis Rheum 2004; 50: 858–65

    PubMed  CAS  Google Scholar 

  70. Hirohata S, Kanai Y, Mitsuo A, et al., NPSLE Research Subcommittee. Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis: a multicenter retrospective study. Clin Rheumatol 2009; 28: 1319–23

    PubMed  Google Scholar 

  71. Okamoto H, Kobayashi A, Yamanaka H. Cytokines and chemokines in neuropsychiatric syndromes of systemic lupus erythematosus. J Biomed Biotechnol. Epub 2010 Jun 29

  72. Aranow C, Diamond B, Mackay M. Glutamate receptor biology and its clinical significance in neuropsychiatric systemic lupus erythematosus. Rheum Dis Clin North Am 2010; 36: 187–201

    PubMed  Google Scholar 

  73. Sabet A, Sibbitt Jr WL, Stidley CA, et al. Neurometabolite markers of cerebral injury in the antiphospholipid antibody syndrome of systemic lupus erythematosus. Stroke 1998; 29: 2254–60

    PubMed  CAS  Google Scholar 

  74. Afeltra A, Garzia P, Mitterhofer AP, et al. Neuropsychiatric lupus syndromes: relationship with antiphospholipid antibodies. Neurology 2003; 61: 108–10

    PubMed  Google Scholar 

  75. Pierangeli SS, Harris EN. Antiphospholipid antibodies in an in vivo thrombosis model in mice. Lupus 1994; 3: 247–51

    PubMed  CAS  Google Scholar 

  76. Katsiari CG, Giavri I, Mitsikostas DD, et al. Acute transverse myelitis and antiphospholipid antibodies in lupus: no evidence for anticoagulation. Eur J Neurol 2011; 18: 556–63

    PubMed  CAS  Google Scholar 

  77. Karassa FB, Afeltra A, Ambrozic A, et al. Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Arthritis Rheum 2006; 54: 312–24

    PubMed  CAS  Google Scholar 

  78. 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: 1357–66

    CAS  Google Scholar 

  79. Ghirardello A, Briani C, Lucchetta M, et al. Anti-ribosomal P protein antibodies and neuropsychiatric systemic lupus erythematosus: cross-sectional vs. prospective studies. Lupus 2010; 19: 771–3

    PubMed  CAS  Google Scholar 

  80. Mostafa GA, Ibrahim DH, Shehab AA, et al. The role of measurement of serum autoantibodies in prediction of pediatric neuropsychiatric systemic lupus erythematosus. J Neuroimmunol 2010; 227: 195–201

    PubMed  CAS  Google Scholar 

  81. Nery FG, Borba EF, Viana VS, et al. Prevalence of depressive and anxiety disorders in systemic lupus erythematosus and their association with anti-ribosomal P antibodies. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 695–700

    PubMed  CAS  Google Scholar 

  82. Bonfa E, Golombek SJ, Kaufman LD, et al. Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med 1987; 317: 265–71

    PubMed  CAS  Google Scholar 

  83. Hanly JG, Urowitz MB, Siannis F, et al. Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: results from an international inception cohort study. Arthritis Rheum 2008; 58: 843–53

    PubMed  CAS  Google Scholar 

  84. Kobiler D, Allweis C. The effect of antisynaptosomal plasma membrane antibodies on memory. Brain Res 1976; 115: 129–38

    PubMed  CAS  Google Scholar 

  85. Morris RG, Anderson E, Lynch GS, et al. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 1986; 319: 774–6

    PubMed  CAS  Google Scholar 

  86. Skerry TM, Genever PG. Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci 2001; 22: 174–81

    PubMed  CAS  Google Scholar 

  87. DeGiorgio LA, Konstantinov KN, Lee SC, et al. A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 2001; 7: 1189–93

    PubMed  CAS  Google Scholar 

  88. 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: 2505–14

    PubMed  CAS  Google Scholar 

  89. Omdal R, Brokstad K, Waterloo K, et al. Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol 2005; 12: 392–8

    PubMed  CAS  Google Scholar 

  90. Emmer BJ, van der Grond J, Steup-Beekman GM, et al. Selective involvement of the amygdala in systemic lupus erythematosus. PLoS Med 2006; 3: e499

    PubMed  Google Scholar 

  91. Hanly JG, Robichaud J, Fisk JD. Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus. J Rheumatol 2006; 33: 1553–8

    PubMed  CAS  Google Scholar 

  92. Harrison MJ, Ravdin LD, Lockshin MD. Relationship between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus. Arthritis Rheum 2006; 54: 2515–22

    PubMed  CAS  Google Scholar 

  93. Steup-Beekman G, Steens S, van Buchem M, et al. Anti-NMDA receptor autoantibodies in patients with systemic lupus erythematosus and their first-degree relatives. Lupus 2007; 16: 329–34

    PubMed  CAS  Google Scholar 

  94. Arinuma Y, Yanagida T, Hirohata S. Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 2008; 58: 1130–5

    PubMed  CAS  Google Scholar 

  95. Yoshio T, Onda K, Nara H, et al. Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 2006; 54: 675–8

    PubMed  CAS  Google Scholar 

  96. Fragoso-Loyo H, Cabiedes J, Orozco-Narvaez A, et al. Serum and cerebrospinal fluid autoantibodies in patients with neuropsychiatric lupus erythematosus: implications for diagnosis and pathogenesis. PLoS One 2008; 3: e3347

    PubMed  Google Scholar 

  97. Conti F, Alessandri C, Bompane D, et al. Autoantibody profile in systemic lupus erythematosus with psychiatric manifestations: a role for antiendothelial-cell Abs. Arthritis Res Ther 2004; 6: 366–72

    Google Scholar 

  98. Song J, Park YB, Lee WK, et al. Clinical associations of anti-endothelial cell Abs in patients with systemic lupus erythematosus. Rheumatol Int 2000; 20: 1–7

    PubMed  CAS  Google Scholar 

  99. Schenatto CB, Xavier RM, Bredemeier M, et al. Raised serum S100B protein levels in neuropsychiatric lupus. Ann Rheum Dis 2006; 65: 829–31

    PubMed  CAS  Google Scholar 

  100. Yang XY, Lin J, Lu XY, et al. Expression of S100B protein levels in serum and cerebrospinal fluid with different forms of neuropsychiatric systemic lupus erythematosus. Clin Rheumatol 2008; 27: 353–7

    PubMed  Google Scholar 

  101. Costallat LT, de Oliveira RM, Santiago MB, et al. Neuropsychiatric manifestations of systemic lupus erythematosus: the value of anticardiolipin, antigangliosides and antigalactocerebrosides antibodies. Clin Rheumatol 1990; 9: 489–97

    PubMed  CAS  Google Scholar 

  102. Jonsen A, Bengtsson AA, Nived O, et al. The heterogeneity of neuropsychiatric systemic lupus erythematosus is reflected in lack of association with cerebrospinal fluid cytokine profiles. Lupus 2003; 12: 846–50

    PubMed  CAS  Google Scholar 

  103. Small P, Mass MF, Kohler PF, et al. Central nervous system involvement in SLE: diagnostic profile and clinical features. Arthritis Rheum 1977; 20: 869–78

    PubMed  CAS  Google Scholar 

  104. Trysberg E, Nylen K, Rosengren LE, et al. Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement. Arthritis Rheum 2003; 48: 2881–7

    PubMed  Google Scholar 

  105. Appenzeller S, Pike GB, Clarke AE. Magnetic resonance imaging in the evaluation of central nervous system manifestations in systemic lupus erythematosus. Clin Rev Allergy Immunol 2008; 34: 361–6

    PubMed  Google Scholar 

  106. Appenzeller S, Rondina JM, Li LM, et al. Cerebral and corpus callosum atrophy in systemic lupus erythematosus. Arthritis Rheum 2005; 52: 2783–9

    PubMed  Google Scholar 

  107. Appenzeller S, Bonilha L, Rio PA, et al. Longitudinal analysis of gray and white matter loss in patients with systemic lupus erythematosus. Neuroimage 2007; 34: 694–701

    PubMed  Google Scholar 

  108. Appenzeller S, Vasconcelos Faria A, Li LM, et al. Quantitative magnetic resonance imaging analyses and clinical significance of hyperintense white matter lesions in systemic lupus erythematosus patients. Ann Neurol 2008; 64: 635–43

    PubMed  Google Scholar 

  109. Luyendijk J, Steens SC, Ouwendijk WJ, et al. Neuropsychiatric SLE: lessons learned from MRI. Arthritis Rheum 2011; 63: 722–32

    PubMed  CAS  Google Scholar 

  110. Rovaris M, Viti B, Ciboddo G, et al. Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry 2000; 68: 170–7

    PubMed  CAS  Google Scholar 

  111. Bosma GP, Rood MJ, Zwinderman AH, et al. Evidence of central nervous system damage in patients with neuropsychiatric systemic lupus erythematosus, demonstrated by magnetization transfer imaging. Arthritis Rheum 2000; 43: 48–54

    PubMed  CAS  Google Scholar 

  112. Moritani T, Shrier DA, Numaguchi Y, et al. Diffusion-weighted echo-planar MR imaging of CNS involvement in systemic lupus erythematosus. Acad Radiol 2001; 8: 741–53

    PubMed  CAS  Google Scholar 

  113. Demaerel P, De Ruyter N, Maes F, et al. Magnetic resonance angiography in suspected cerebral vasculitis. Eur Radiol 2004; 14: 1005–12

    PubMed  Google Scholar 

  114. Efthimiou P, Blanco M. Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers. Mod Rheumatol 2009; 19: 457–68

    PubMed  CAS  Google Scholar 

  115. Sanna G, Bertolaccini ML, Mathieu A. Central nervous system lupus: a clinical approach to therapy. Lupus 2003; 12: 935–42

    PubMed  CAS  Google Scholar 

  116. Barile-Fabris L, Ariza-Andraca R, Olguin-Ortega L, et al. Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann Rheum Dis 2005; 64: 620–5

    PubMed  CAS  Google Scholar 

  117. 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; 115:59–62

    PubMed  CAS  Google Scholar 

  118. Cuadrado MJ, Khamashta MA, Ballesteros A, et al. Can neurologic manifestations of Hughes (antiphospholipid) syndrome be distinguished from multiple sclerosis? Analysis of 27 patients and review of the literature. Medicine (Baltimore) 2000; 79: 57–68

    CAS  Google Scholar 

  119. 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: 432–9

    PubMed  CAS  Google Scholar 

  120. Chatham WW, Kimberly RP. Treatment of lupus with corticosteroids. Lupus 2001; 10: 140–7

    PubMed  CAS  Google Scholar 

  121. Boumpas DT, Yamada H, Patronas NJ, et al. Pulse cyclophosphamide for severe neuropsychiatric lupus. Q J Med 1991; 81: 975–84

    PubMed  CAS  Google Scholar 

  122. Takada K, Illei GG, Boumpas DT. Cyclophosphamide for the treatment of systemic lupus erythematosus. Lupus 2001; 10: 154–61

    PubMed  CAS  Google Scholar 

  123. Ramos PC, Mendez MJ, Ames PR, et al. Pulse cyclophosphamide in the treatment of neuropsychiatric systemic lupus erythematosus. Clin Exp Rheumatol 1996; 14: 295–9

    PubMed  CAS  Google Scholar 

  124. Sakic B, Kolb B, Whishaw IQ, et al. Immunosuppression prevents neuronal atrophy in lupus-prone mice: evidence for brain damage induced by autoimmune disease? J Neuroimmunol 2000; 111: 93–101

    PubMed  CAS  Google Scholar 

  125. Xu J, Cheng Y, Chai P, et al. White-matter volume reduction and the protective effect of immunosuppressive therapy in systemic lupus erythematosus patients with normal appearance by conventional magnetic resonance imaging. Rheumatol 2010; 37: 974–86

    Google Scholar 

  126. Schroeder JO, Euler HH. Treatment combining plasmapheresis and pulse cyclophosphamide in severe systemic lupus erythematosus. Adv Exp Med Biol 1989; 260: 203–13

    PubMed  CAS  Google Scholar 

  127. Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med 2001; 345: 747–55

    PubMed  CAS  Google Scholar 

  128. Hughes RA, Raphael JC, Swan AV, et al. Intravenous immunoglobulin for Guillain-Barre syndrome. Cochrane Database Syst Rev 2001; (2): CD002063

  129. Sherer Y, Levy Y, Langevitz P, et al. Successful treatment of systemic lupus erythematosus cerebritis with intravenous immunoglobulin. Clin Rheumatol 1999; 18: 170–3

    PubMed  CAS  Google Scholar 

  130. Tomer Y, Shoenfeld Y. Successful treatment of psychosis secondary to SLE with high dose intravenous immunoglobulin. Clin Exp Rheumatol 1992; 10: 391–3

    PubMed  CAS  Google Scholar 

  131. Valesini G, Priori R, Francia A, et al. Central nervous system involvement in systemic lupus erythematosus: a new therapeutic approach with intrathecal dexamethasone and methotrexate. Springer Semin Immunopathol 1994; 16: 313–21

    PubMed  CAS  Google Scholar 

  132. Dong Y, Zhang X, Tang F, et al. Intrathecal injection with methotrexate plus dexamethasone in the treatment of central nervous system involvement in systemic lupus erythematosus. Chin Med J (Engl) 2001; 114: 764–6

    CAS  Google Scholar 

  133. Grisanti M, Nader A, Cacciuttolo R. Central nervous system involvement due to systemic lupus erythematosus/antiphospholipid syndrome: successful treatment with mycophenolate mofetil. Lupus 2001; 10: S31

    Google Scholar 

  134. Dall’Era M, Wofsy D. Biologic therapy for systemic lupus erythematosus. Discov Med 2010; 9: 20–3

    PubMed  Google Scholar 

  135. Tokunaga M, Saito K, Kawabata D, et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis 2007; 66: 470–5

    PubMed  CAS  Google Scholar 

  136. Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum 2010; 62: 222–33

    PubMed  CAS  Google Scholar 

  137. Murray E, Perry M. Off-label use of rituximab in systemic lupus erythematosus: a systematic review. Clin Rheumatol 2010; 29: 707–16

    PubMed  Google Scholar 

  138. Turner-Stokes T, Lu TY, Ehrenstein MR, et al. The efficacy of repeated treatment with B-cell depletion therapy in systemic lupus erythematosus: an evaluation. Rheumatology (Oxford) 2011; 50: 1401–8

    CAS  Google Scholar 

  139. Genentech, Inc. and Biogen Idec. Study of Rituxan (rituximab) in lupus nephritis misses primary endpoint [online]. Available from URL: http://www.newsmedical.net/news/2009/03/11/46787.aspx [Accessed 2011 Jul 4]

  140. Heinlein AC, Gertner E. Marked inflammation in catastrophic longitudinal myelitis associated with systemic lupus erythematosus. Lupus 2007; 16: 823–6

    PubMed  CAS  Google Scholar 

  141. Crowther MA, Ginsberg JS, Julian J, 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 2003; 349: 1133–8

    PubMed  CAS  Google Scholar 

  142. Ruiz-Irastorza G, Hunt BJ, Khamashta MA. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum 2007; 57: 1487–95

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Rheumatology Unit, Faculty of Medical Science, State University of Campinas, Campinas, SP, Brazil, CEP 13083-970

    Mariana Postal, Lilian T. L. Costallat &  Simone Appenzeller

Authors
  1. Mariana Postal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lilian T. L. Costallat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simone Appenzeller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simone Appenzeller.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Postal, M., Costallat, L.T.L. & Appenzeller, S. Neuropsychiatric Manifestations in Systemic Lupus Erythematosus. CNS Drugs 25, 721–736 (2011). https://doi.org/10.2165/11591670-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11591670-000000000-00000

Keywords

Search

Navigation