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Neurocognitive impairment in children and adolescents with systemic lupus erythematosus

Nature Clinical Practice Rheumatology volume 5, pages 106–114 (2009)Cite this article

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, in which neuropsychiatric manifestations are a common cause of significant morbidity. The American College of Rheumatology has identified 19 distinct neuropsychiatric syndromes associated with SLE, although the 1982 American College of Rheumatology classification criteria for SLE recognize only two: seizures and psychosis. Neurocognitive impairment (NCI) is one of the most common and clinically challenging manifestations of SLE, but its pathophysiology remains poorly understood. This Review examines the epidemiology and pathophysiology of NCI in children and adolescents with SLE, as well as the diagnostic and therapeutic approaches that are available for these patients. As few published studies specifically address NCI in pediatric SLE, new directions for research are also discussed.

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References

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

  2. Sibbitt WL Jr et al. (2002) The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus. J Rheumatol 29: 1536–1542

    Google Scholar 

  3. Hiraki LT et al. (2008) Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. J Pediatr 152: 550–556

    Article  Google Scholar 

  4. Brunner HI et al. (2007) Initial validation of the Pediatric Automated Neuropsychological Assessment Metrics for childhood-onset systemic lupus erythematosus. Arthritis Rheum 57: 1174–1182

    Article  Google Scholar 

  5. Mikdashi JA et al. (2007) Proposed response criteria for neurocognitive impairment in systemic lupus erythematosus clinical trials. Lupus 16: 418–425

    Article  Google Scholar 

  6. Ainiala H et al. (2001) The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 57: 496–500

    Article  CAS  Google Scholar 

  7. Glanz BI et al. (1997) Pattern of neuropsychologic dysfunction in inactive systemic lupus erythematosus. Neuropsychiatry Neuropsychol Behav Neurol 10: 232–238

    CAS  PubMed  Google Scholar 

  8. Denburg SD et al. (1987) Cognitive impairment in systemic lupus erythematosus: a neuropsychological study of individual and group deficits. J Clin Exp Neuropsychol 9: 323–339

    Article  CAS  Google Scholar 

  9. Kozora E et al. (1996) Analysis of cognitive and psychological deficits in systemic lupus erythematosus patients without overt central nervous system disease. Arthritis Rheum 39: 2035–2045

    Article  CAS  Google Scholar 

  10. Shucard JL et al. (2004) Working memory and processing speed deficits in systemic lupus erythematosus as measured by the paced auditory serial addition test. J Int Neuropsychol Soc 10: 35–45

    Article  Google Scholar 

  11. Ginsburg KS et al. (1992) A controlled study of the prevalence of cognitive dysfunction in randomly selected patients with systemic lupus erythematosus. Arthritis Rheum 35: 776–782

    Article  CAS  Google Scholar 

  12. Hanly JG et al. (1992) Cognitive impairment in patients with systemic lupus erythematosus. J Rheumatol 19: 562–567

    CAS  PubMed  Google Scholar 

  13. McLaurin EY et al. (2005) Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology 64: 297–303

    Article  CAS  Google Scholar 

  14. Harel L et al. (2006) Neuropsychiatric manifestations in pediatric systemic lupus erythematosus and association with antiphospholipid antibodies. J Rheumatol 33: 1873–1877

    CAS  PubMed  Google Scholar 

  15. Avcin T et al. (2008) A followup study of antiphospholipid antibodies and associated neuropsychiatric manifestations in 137 children with systemic lupus erythematosus. Arthritis Rheum 59: 206–213

    Article  Google Scholar 

  16. Emori A et al. (2005) Cognitive dysfunction in systemic lupus erythematosus. Psychiatry Clin Neurosci 59: 584–589

    Article  Google Scholar 

  17. Benedict RH et al. (2008) Neuropsychological impairment in systemic lupus erythematosus: a comparison with multiple sclerosis. Neuropsychol Rev 18: 149–166

    Article  CAS  Google Scholar 

  18. Carbotte RM et al. (1995) Cognitive deficit associated with rheumatic diseases: neuropsychological perspectives. Arthritis Rheum 38: 1363–1374

    Article  CAS  Google Scholar 

  19. Wyckoff PM et al. (1995) Neuropsychological assessment of children and adolescents with systemic lupus erythematosus. Lupus 4: 217–220

    Article  CAS  Google Scholar 

  20. Ardoin SP et al. (2008) Retrospective analysis of neurocognitive testing in children and adolescents with SLE. Arthritis Rheum (in press)

  21. Filley CM (2005) White matter and behavioral neurology. Ann NY Acad Sci 1064: 162–183

    Article  Google Scholar 

  22. Filley CM (1998) The behavioral neurology of cerebral white matter. Neurology 50: 1535–1540

    Article  CAS  Google Scholar 

  23. Luna B et al. (2004) Maturation of cognitive processes from late childhood to adulthood. Child Dev 75: 1357–1372

    Article  Google Scholar 

  24. Luna B and Sweeney JA (2001) Studies of brain and cognitive maturation through childhood and adolescence: a strategy for testing neurodevelopmental hypotheses. Schizophr Bull 27: 443–455

    Article  CAS  Google Scholar 

  25. Korkman M et al. (2001) Effects of age on neurocognitive measures of children ages 5 to 12: a cross-sectional study on 800 children from the United States. Dev Neuropsychol 20: 331–354

    Article  CAS  Google Scholar 

  26. Devinsky O et al. (1988) Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura. Ann Neurol 23: 380–384

    Article  CAS  Google Scholar 

  27. Ellis SG and Verity MA (1979) Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955–1977. Semin Arthritis Rheum 8: 212–221

    Article  CAS  Google Scholar 

  28. Kang EH et al. (2008) Flow cytometric assessment of anti-neuronal antibodies in central nervous system involvement of systemic lupus erythematosus and other autoimmune diseases. Lupus 17: 21–25

    Article  CAS  Google Scholar 

  29. Papero PH et al. (1990) Neuropsychologic deficits and antineuronal antibodies in pediatric systemic lupus erythematosus. Clin Exp Rheumatol 8: 417–424

    CAS  PubMed  Google Scholar 

  30. Zandman-Goddard G et al. (2007) Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome. Semin Arthritis Rheum 36: 297–315

    Article  CAS  Google Scholar 

  31. Benseler SM and Silverman ED (2007) Neuropsychiatric involvement in pediatric systemic lupus erythematosus. Lupus 16: 564–571

    Article  CAS  Google Scholar 

  32. Toubi E and Shoenfeld Y (2007) Clinical and biological aspects of anti-P-ribosomal protein autoantibodies. Autoimmun Rev 6: 119–125

    Article  CAS  Google Scholar 

  33. Katzav A et al. (2007) Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system. Arthritis Rheum 56: 938–948

    Article  CAS  Google Scholar 

  34. Hanly JG et al. (1999) A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum 42: 728–734

    Article  CAS  Google Scholar 

  35. DeGiorgio LA et al. (2001) A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 7: 1189–1193

    Article  CAS  Google Scholar 

  36. Kowal C et al. (2004) Cognition and immunity; antibody impairs memory. Immunity 21: 179–188

    Article  CAS  Google Scholar 

  37. Yoshio T et al. (2006) Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 54: 675–678

    Article  CAS  Google Scholar 

  38. Levy D (2007) Anti-NR-2 antibodies are prevalent in childhood-onset SLE (cSLE), but do not predict neurocognitive dysfunction [abstract]. Arthritis Rheum 55: S143

    Google Scholar 

  39. Iikuni N et al. (2006) Raised monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebrospinal fluid of patients with neuropsychiatric lupus. Ann Rheum Dis 65: 253–256

    Article  CAS  Google Scholar 

  40. Fragoso-Loyo H et al. (2007) Interleukin-6 and chemokines in the neuropsychiatric manifestations of systemic lupus erythematosus. Arthritis Rheum 56: 1242–1250

    Article  CAS  Google Scholar 

  41. Hanly JG et al. (2005) Neuropsychiatric syndromes in patients with systemic lupus erythematosus and rheumatoid arthritis. J Rheumatol 32: 1459–1466

    PubMed  Google Scholar 

  42. Ouvrier RA et al. (1993) The value of the Mini-Mental State Examination in childhood: a preliminary study. J Child Neurol 8: 145–148

    Article  CAS  Google Scholar 

  43. Brunner HI et al. (2008) Standardizing the neuropsychological evaluation of children with SLE [abstract]. Lupus 17: 467

    Google Scholar 

  44. Levy DM et al. (2007) Neurocognitive function in childhood-onset systemic lupus erythematosus [abstract]. Arthritis Rheum 56: S368

    Google Scholar 

  45. Reeves DL et al. (2007) ANAM genogram: historical perspectives, description, and current endeavors. Arch Clin Neuropsychol 22 (Suppl 1): S15–S37

    Article  Google Scholar 

  46. Kane RL et al. (2007) Identifying and monitoring cognitive deficits in clinical populations using Automated Neuropsychological Assessment Metrics (ANAM) tests. Arch Clin Neuropsychol 22 (Suppl 1): S115–S126

    Article  Google Scholar 

  47. Roebuck-Spencer TM et al. (2006) Use of computerized assessment to predict neuropsychological functioning and emotional distress in patients with systemic lupus erythematosus. Arthritis Rheum 55: 434–441

    Article  Google Scholar 

  48. Holliday SL et al. (2003) Validating a computerized neuropsychological test battery for mixed ethnic lupus patients. Lupus 12: 697–703

    Article  CAS  Google Scholar 

  49. Sibbitt WL Jr et al. (1999) Neuroimaging in neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 42: 2026–2038

    Article  Google Scholar 

  50. Jennings JE et al. (2004) Value of MRI of the brain in patients with systemic lupus erythematosus and neurologic disturbance. Neuroradiology 46: 15–21

    Article  CAS  Google Scholar 

  51. Ainiala H et al. (2005) Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population-based study. Scand J Rheumatol 34: 376–382

    Article  CAS  Google Scholar 

  52. Kozora E et al. (1998) Magnetic resonance imaging abnormalities and cognitive deficits in systemic lupus erythematosus patients without overt central nervous system disease. Arthritis Rheum 41: 41–47

    Article  CAS  Google Scholar 

  53. Kao CH et al. (1999) The role of FDG-PET, HMPAO-SPET and MRI in the detection of brain involvement in patients with systemic lupus erythematosus. Eur J Nucl Med 26: 129–134

    Article  CAS  Google Scholar 

  54. Weiner SM et al. (2000) Diagnosis and monitoring of central nervous system involvement in systemic lupus erythematosus: value of F-18 fluorodeoxyglucose PET. Ann Rheum Dis 59: 377–385

    Article  CAS  Google Scholar 

  55. Sabbadini MG et al. (1999) Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations. Lupus 8: 11–19

    Article  CAS  Google Scholar 

  56. Waterloo K et al. (2001) Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow. J Neurol 248: 595–602

    Article  CAS  Google Scholar 

  57. Kozora E et al. (2005) Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data. Cogn Behav Neurol 18: 159–162

    Article  Google Scholar 

  58. Brooks WM et al. (1999) Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus. J Rheumatol 26: 81–85

    CAS  PubMed  Google Scholar 

  59. Bosma GP et al. (2000) Detection of cerebral involvement in patients with active neuropsychiatric systemic lupus erythematosus by the use of volumetric magnetization transfer imaging. Arthritis Rheum 43: 2428–2436

    Article  CAS  Google Scholar 

  60. Rovaris M et al. (2000) Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry 68: 170–177

    Article  CAS  Google Scholar 

  61. Emmer BJ et al. (2006) Detection of change in CNS involvement in neuropsychiatric SLE: a magnetization transfer study. J Magn Reson Imaging 24: 812–816

    Article  Google Scholar 

  62. Emmer BJ et al. (2008) Correlation of magnetization transfer ratio histogram parameters with neuropsychiatric systemic lupus erythematosus criteria and proton magnetic resonance spectroscopy: association of magnetization transfer ratio peak height with neuronal and cognitive dysfunction. Arthritis Rheum 58: 1451–1457

    Article  CAS  Google Scholar 

  63. DiFrancesco MW et al. (2007) Functional magnetic resonance imaging assessment of cognitive function in childhood-onset systemic lupus erythematosus: a pilot study. Arthritis Rheum 56: 4151–4163

    Article  Google Scholar 

  64. Naqibuddin M et al. (2007) Memantine in systemic lupus erythematosus: a randomized double-blind, placebo-controlled trial [abstract]. Arthritis Rheum 56 (Suppl 9): S528

    Google Scholar 

  65. Harrison MJ et al. (2005) Results of intervention for lupus patients with self-perceived cognitive difficulties. Neurology 65: 1325–1327

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This publication was made possible by Grant Number 5K23AR53202 from National Institutes of Arthritis and Musculoskeletal and Skin Diseases.

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. DM Levy is an Assistant Professor in the Division of Rheumatology at the Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University Medical Center, New York, NY,

    Deborah M Levy

  2. SP Ardoin is a Clinical Associate in the Divisions of Adult and Pediatric Rheumatology, and LE Schanberg is co-Chief and Associate Professor in the Division of Pediatric Rheumatology at Duke University Medical Center, Durham, NC, USA.,

    Stacy P Ardoin & Laura E Schanberg

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Correspondence to Laura E Schanberg.

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Levy, D., Ardoin, S. & Schanberg, L. Neurocognitive impairment in children and adolescents with systemic lupus erythematosus. Nat Rev Rheumatol 5, 106–114 (2009). https://doi.org/10.1038/ncprheum0988

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