Advertisement

Diagnosis and Differential Diagnosis

  • Taku Yoshio
  • Hiroshi Okamoto
Chapter

Abstract

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a life-threatening disorder and early diagnosis and proper treatment are critical for the management of patients with this disease. NPSLE 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 NPSLE events 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 NPSLE events are a consequence either of autoantibodies and inflammatory mediators, or of microvasculopathy and thrombosis. Diagnosis of NPSLE requires the exclusion of other causes, and clinical assessment directs the selection of appropriate examinations. These examinations include measurement of autoantibodies, analysis of cerebrospinal fluid, electrophysiological studies, neuropsychological assessment and neuroimaging to evaluate brain structure and function. This chapter reviews the important key points for the correct diagnosis and the differential diagnosis.

Keywords

NPSLE Diagnosis Differential diagnosis Corticosteroid-induced psychiatric disorders (CIPD) Autoantibodies Cytokines Chemokines 

References

  1. 1.
    Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365:2110–21.CrossRefPubMedGoogle Scholar
  2. 2.
    Jeltsch-David H, Muller S. Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat Rev Neurol. 2014;10:579–96.CrossRefPubMedGoogle Scholar
  3. 3.
    Zirkzee EJ, et al. Prospective study of clinical phenotypes in neuropsychiatric systemic lupus erythematosus; multidisciplinary approach to diagnosis and therapy. J Rheumatol. 2012;39:2118–26.CrossRefPubMedGoogle Scholar
  4. 4.
    The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999; 42:599–608.Google Scholar
  5. 5.
    Hanly JG, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Andrade RM, et al. Seizures in patients with systemic lupus erythematosus: data from LUMINA, a multiethnic cohort (LUMINA LIV). Ann Rheum Dis. 2008;67:829–34.CrossRefPubMedGoogle Scholar
  7. 7.
    Mikdashi J, Handwerger B. Predictors of neuropsychiatric damage in systemic lupus erythematosus: data from the Maryland lupus cohort. Rheumatology. 2004;43:1555–60.CrossRefPubMedGoogle Scholar
  8. 8.
    Tomietto P, et al. General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Rheum. 2007;57:1461–72.CrossRefPubMedGoogle Scholar
  9. 9.
    Appenzeller S, et al. Epileptic seizures in systemic lupus erythematosus. Neurology. 2004;63:1808–12.CrossRefPubMedGoogle Scholar
  10. 10.
    Buján S, et al. Contribution of the initial features of systemic lupus erythematosus to the clinical evolution and survival of a cohort of Mediterranean patients. Ann Rheum Dis. 2003;62:859–65.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mikdashi J, et al. Factors at diagnosis predict subsequent occurrence of seizures in systemic lupus erythematosus. Neurology. 2005;64:2102–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Sanna G, et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol. 2003;30:985–92.PubMedGoogle Scholar
  13. 13.
    Mok MY, et al. Antiphospholipid antibody profiles and their clinical associations in Chinese patients with systemic lupus erythematosus. J Rheumatol. 2005;32:622–8.PubMedGoogle Scholar
  14. 14.
    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). 2012;51:157–68.CrossRefGoogle Scholar
  15. 15.
    Florica B, et al. Peripheral neuropathy in patients with systemic lupus erythematosus. Semin Arthritis Rheum. 2011;41:203–11.CrossRefPubMedGoogle Scholar
  16. 16.
    Toledano P, et al. Neuropsychiatric systemic lupus erythematosus: magnetic resonance imaging findings and correlation with clinical and immunological features. Autoimmun Rev. 2013;12:1166–70.CrossRefPubMedGoogle Scholar
  17. 17.
    Jarpa E, et al. Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity. Lupus. 2011;20:58–66.CrossRefPubMedGoogle Scholar
  18. 18.
    Shimojima Y, et al. Relationship between clinical factors and neuropsychiatric manifestations in systemic lupus erythematosus. Clin Rheumatol. 2005;24:469–75.CrossRefPubMedGoogle Scholar
  19. 19.
    Morrison E, et al. Neuropsychiatric systemic lupus erythematosus: association with global disease activity. Lupus. 2014;23:370–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Bertsias G, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR Standing Committee for International Clinical Studies including therapeutics. Ann Rheum Dis. 2008;67:195–205.CrossRefPubMedGoogle Scholar
  21. 21.
    Bertsias GK, 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;69:195–205.Google Scholar
  22. 22.
    West SG, et al. Neuropsychiatric lupus erythematosus: a 10-year prospective study on the value of diagnostic tests. Am J Med. 1995;99:153–63.CrossRefPubMedGoogle Scholar
  23. 23.
    Zandman-Goddard G, et al. Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome. Semin Arthritis Rheum. 2007;36:297–315.CrossRefPubMedGoogle Scholar
  24. 24.
    Kimura A, et al. Antibodies in patients with neuropsychiatric systemic lupus erythematosus. Neurology. 2010;74:1372–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Hanley JG, 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.CrossRefGoogle Scholar
  26. 26.
    West S. The nervous system. In: Wallace DJ, Hahn BH, editors. Dubοis’ lupus erythematosus. 7th ed. Phiadelphia: Lippincott-Williams & Wilkins; 2007. p. 707–46.Google Scholar
  27. 27.
    Hirohata S, Taketani TA. Serial study of changes in intrathecal immunoglobulin synthesis in a patient with central nervous system systemic lupus erythematosus. J Rheumatol. 1987;14:1055–7.PubMedGoogle Scholar
  28. 28.
    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;41:1819–27.CrossRefPubMedGoogle Scholar
  29. 29.
    Bluestein HG, et al. Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus. Am J Med. 1981;70:240–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Okamoto H, et al. Cytokines and chemokines in neuropsychiatric syndromes of systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:268436.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Yoshio T, et al. IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus. Lupus. 2016;25:997–1003.CrossRefPubMedGoogle Scholar
  32. 32.
    Aranow C, et al. Pathogenesis of the nervous system. In: Wallace DJ, Hahn BH, editors. Dubοis’ lupus erythematosus. 8th ed. Philadelphia: Lippincott-Williams & Wilkins; 2013. p. 363–7.Google Scholar
  33. 33.
    Okamoto H, et al. IP-10/MCP-1 ratio in CSF is an useful diagnostic marker of neuropsychiatric lupus patients. Rheumatology. 2006;45:232–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Kozora E, et al. Magnetic resonance imaging abnormalities and cognitive deficits in systemic lupus erythematosus patients without overt central nervous system disease. Arthritis Rheum. 1998;41:41–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Nomura K, et al. Asymptomatic cerebrovascular lesions detected by magnetic resonance imaging in patients with systemic lupus erythematosus lacking a history of neuropsychiatric events. Intern Med. 1999;38:785–95.CrossRefPubMedGoogle Scholar
  36. 36.
    Sibbitt WL, et al. Magnetic resonance and computed tomographic imaging in the evaluation of acute neuropsychiatric disease in systemiclupus erythematosus. Ann Rheum Dis. 1989;48:1014–22.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Appenzeller S, et al. Evidence of reversible axonal dysfunction in systemic lupus erythematosus: a proton MRS study. Brain. 2005;128(Pt 12):2933–40.CrossRefPubMedGoogle Scholar
  38. 38.
    Axford JS, et al. Sensitivity of quantitative (1) H magnetic resonance spectroscopy of the brain in detecting early neuronal damage in systemic lupus erythematosus. Ann Rheum Dis. 2001;60:106–11.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Bosma GP, et al. Multisequence magnetic resonance imaging study of neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 2004;50:3195–202.CrossRefPubMedGoogle Scholar
  40. 40.
    Steens SC, et al. Selective gray matter damage in neuropsychiatric lupus. Arthritis Rheum. 2004;50:2877–81.CrossRefPubMedGoogle Scholar
  41. 41.
    Hughes M, et al. Diffusion tensor imaging in patients with acute onset of neuropsychiatric systemic lupus erythematosus: a prospective study of apparent diffusion coefficient, fractional anisotropy values, and eigenvalues in different regions of the brain. Acta Radiol. 2007;48:213–22.CrossRefPubMedGoogle Scholar
  42. 42.
    Castellino G, et al. Single photon emission computed tomography and magnetic resonance imaging evaluation in SLE patients with and without neuropsychiatric involvement. Rheumatology. 2008;47:319–23.CrossRefPubMedGoogle Scholar
  43. 43.
    Zhang X, et al. Diagnostic value of single-photon-emission computed tomography in severe central nervous system involvement of systemic lupus erythematosus: a case-control study. Arthritis Rheum. 2005;53:845–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Weiner SM, et al. Diagnosis and monitoring of central nervous system involvement in systemic lupus erythematosus: value of F-18 fluorodeoxyglucose PET. Ann Rheum Dis. 2000;59:377–85.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Fragoso-Loyo H, et al. Inflammatory profile in cerebrospinal fluid of patients with headache as a manifestation of neuropsychiatric systemic lupus erythematosus. Rheumatology. 2013;52:2218–22.CrossRefPubMedGoogle Scholar
  46. 46.
    Mitsikostas DD, et al. A meta-analysis for headache in systemic lupus erythematosus: the evidence and the myth. Brain. 2004;127(Pt 5):1200–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Tomietto P, et al. General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Rheum. 2007;57:1461–72.CrossRefPubMedGoogle Scholar
  48. 48.
    Panopalis P, et al. Impact of memory impairment on employment status in persons with systemic lupus erythematosus. Arthritis Rheum. 2007;57:1453–60.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ainiala H, et al. Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population-based study. Scand J Rheumatol. 2005;34:376–82.CrossRefPubMedGoogle Scholar
  50. 50.
    Lapteva L, et al. Anti-N-methyl-d-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum. 2006;54:2505–14.CrossRefPubMedGoogle Scholar
  51. 51.
    Waterloo K, et al. Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow. J Neurol. 2001;248:595–602.CrossRefPubMedGoogle Scholar
  52. 52.
    Appenzeller S, et al. Epileptic seizures in systemic lupus erythema- tosus. Neurology. 2004;63:1808–12.CrossRefPubMedGoogle Scholar
  53. 53.
    González-Duarte A, et al. Clinical description of seizures in patients with systemic lupus erythematosus. Eur Neurol. 2008;59:320–3.CrossRefPubMedGoogle Scholar
  54. 54.
    Tokunaga M, et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis. 2007;66:470–5.CrossRefPubMedGoogle Scholar
  55. 55.
    Briani C, et al. Neurolupus is associated with anti-ribosomal P protein antibodies: an inception cohort study. J Autoimmun. 2009;32:79–84.CrossRefPubMedGoogle Scholar
  56. 56.
    Hanly JG, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Karassa FB, 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.CrossRefPubMedGoogle Scholar
  58. 58.
    Kodama K, et al. Single photon emission computed tomography in systemic lupus erythematosus with psychiatric symptoms. J Neurol Neurosurg Psychiatry. 1995;58:307–11.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Birnbaum J, et al. Distinct subtypes of myelitis in systemic lupus erythematosus. Arthritis Rheum. 2009;60:3378–87.CrossRefPubMedGoogle Scholar
  60. 60.
    Pittock SJ, et al. Neuromyelitis optica and non organ-specific autoimmunity. Arch Neurol. 2008;65:78–83.PubMedGoogle Scholar
  61. 61.
    Tseng MT, et al. Skin denervation and cutaneous vasculitis in systemic lupus erythematosus. Brain. 2006;129(Pt 4):977–85.CrossRefPubMedGoogle Scholar
  62. 62.
    Chau SY, Mok CC. Factors predictive of corticosteroid psychosis in patients with systemic lupus erythematosus. Neurology. 2003;61:104–7.CrossRefPubMedGoogle Scholar
  63. 63.
    Nishimura K, et al. New-onset psychiatric disorders after corticosteroid therapy in systemic lupus erythematosus: an observational case-series study. J Neurol. 2014;261:2150–8.CrossRefPubMedGoogle Scholar
  64. 64.
    Katsumata Y, et al. Diagnostic reliability of cerebral spinal fluid tests for acute confusional state (delirium) in patients with systemic lupus erythematosus: interleukin 6 (IL-6), IL-8, interferon-alpha, IgG index, and Q-albumin. J Rheumatol. 2007;34:2010–7.PubMedGoogle Scholar
  65. 65.
    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. 2007;57:347–51.CrossRefPubMedGoogle Scholar
  66. 66.
    Waters P, et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol. 2008;65:913–9.CrossRefPubMedGoogle Scholar
  67. 67.
    Lennon VA, et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005;202:473–7.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Budhoo A, Mody GM. The spectrum of posterior reversible encephalopathy in systemic lupus erythematosus. Clin Rheumatol. 2015;34:2127–34.CrossRefPubMedGoogle Scholar
  69. 69.
    Calabrese LH, et al. M. Progressive multifocal leukoencephalopathy in rheumatic diseases: evolving clinical and pathologic patterns of disease. Arthritis Rheum. 2007;56:2116–28.CrossRefPubMedGoogle Scholar
  70. 70.
    De Gascun CF, Carr MJ. Human polyomavirus r eactivation: disease pathogenesis and treatment approaches. Clin Dev Immunol. 2013;2013:373579.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Cinque P, et al. Progressive multifocal leukoencephalopathy in HIV-1 infection. Lancet Infect Dis. 2009;9:625–36.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    d’Arminio Monforte A, et al. A comparison of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients. J Neurol. 1997;244:35–9.CrossRefPubMedGoogle Scholar
  73. 73.
    Garrels K, et al. Progressive multifocal leukoencephalopathy: clinical and MR response to treatment. AJNR Am J Neuroradiol. 1996;17:597–600.PubMedGoogle Scholar
  74. 74.
    Smith AB, et al. From the archives of the AFIP: central nervous system infections associated with human immunodeficiency virus infection: radiologic-pathologic correlation. Radiographics. 2008;28:2033–58.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Rheumatology and Clinical ImmunologySchool of Medicine, Jichi Medical UniversityShimotsuke-shiJapan
  2. 2.Minami-otsuka institute of technology, Minami-otsuka ClinicTokyoJapan

Personalised recommendations