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Egyptian Rheumatology and Rehabilitation
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Subclinical neuropsychiatric dysfunctions in female patients with systemic lupus erythematosus

Egyptian Rheumatology and Rehabilitation volume 45, pages 49–56 (2018)Cite this article

Abstract

Objective

To examine for presence of subclinical neuropsychiatric lupus and cerebral atherosclerosis and their correlation with MRI/magnetic resonance angiography (MRA) findings and disease activity and to find if these radiological changes compared with laboratory parameters could be predictive of the early NP affection aiming for early management of these dysfunctions.

Patients and methods

Thirty adult female patients with systemic lupus erythematosus (SLE) were enrolled, with assessment of SLE disease activity using Systemic Lupus Erythematosus Disease Activity Index; psychometric evaluations using the Modified Mini-Mental State Examination to assess for cognitive dysfunction; Hamilton Depression Rating Scale and Hamilton Anxiety Scale to assess for depression and anxiety, respectively; and brain MRI/MRA to detect any changes in subclinical cases.

Results

The mean age was 31.7 years. Twelve (40%) patients had positive antiphospholipid (aPL) antibodies with or without clinically evident antiphospholipid syndrome, 22 (73.33%) had different NP manifestations, 13 (43.3%) depression, 15 (50%) anxiety, and 16 (53.3%) cognitive dysfunction. All patients with depression and anxiety and 87.5% of patients with dementia showed abnormalities on MRI. All patients with positive aPL showed abnormalities on MRI, whereas abnormalities on MRI were found in only eight patients with SLE with negative aPL (100 vs. 44.4%). There was a significant correlation between SLE disease activity and both NP manifestations and abnormalities on MRI/MRA, and also between aPL antibodies and NP manifestations. Abnormalities on MRI included discrete white matter lesions, cortical atrophy, and gross infarctions.

Conclusion

Significant number of patients with SLE without overt NP manifestations had subclinical cerebrovascular and cognitive dysfunctions, depression, and anxiety by simple bedside questionnaires. SLE disease activity positively correlates with NP manifestations. The presence of aPL antibodies is a strong risk factor for developing NP SLE. Several distinct brain MRI patterns were observed in patients with active NP SLE, suggestive of different pathogenic mechanisms.

References

  1. Hahn B. Lupus eritematoso sistemico. In Fauci AS, Braunwald E, Kasper DL, editors. Harrison medicina interna. 17th ed. Rio de Janeiro: McGraw-Hill Interamericana do Brasil; 2008. pp. 2075–2083

    Google Scholar 

  2. Kozora E, Erkan D, West SG, Filley CM, Zhang L, Ramon G, et al. Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE). Lupus 2013; 22:73–80

    Article  CAS  Google Scholar 

  3. Pamfil C, Fanouriakis A, Damian L, Rinzis M, Sidiropoulos P, Tsivgoulis G, et al. EULAR recommendations for neuropsychiatric systemic lupus erythematosus vs. usual care: results from two European centres. Rheumatology (Oxford) 2015; 54:1270–1278

    CAS  Google Scholar 

  4. Anselm Mak A, Man Ho RC, Lau CS. Clinical implications of neuropsychiatric systemic lupus erythematosus. Adv Psychiatr Treat 2009; 15:451–458

    Article  Google Scholar 

  5. Hanly JG. Diagnosis and management of neuropsychiatric SLE. Nat Rev Rheumatol 2014; 10:338–347

    Article  CAS  Google Scholar 

  6. Magro-Checa C, Zirkzee EJ, Huizinga TM, Steup-Beekman GM. Management of neuropsychiatric systemic lupus erythematosus: current approaches and future perspectives. Drugs 2016; 76:459–483

    Article  CAS  Google Scholar 

  7. Liang M, Corzillius M, Bae S, Lew RA, Fortin PR, Gordon C. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42:599–608

    Article  Google Scholar 

  8. Hirohata S, Sakuma Y, Yanagida T, Yoshio T. Association of cerebrospinal fluid anti-Sm antibodies with acute confusional state in systemic lupus erythematosus. Arthritis Res Ther 2014; 16:450

    Article  Google Scholar 

  9. Bertsias G, Ioannidis J, Aringer M, Bollen E, Bombardieri S, Bruce IN, 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: 2074–2082

    Article  CAS  Google Scholar 

  10. Petri M, Orbai A, Alarcón G, Gordon C, Merrill J, Fortin P, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64:2677–2686

    PubMed  PubMed Central  Google Scholar 

  11. Bombardier C, Gladman D, Urowitz M, Caron D, Chang C, Austin A, et al. Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum 1992; 35:630–640

    CAS  PubMed  Google Scholar 

  12. Folstein M, Folstein S, McHugh P. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–198

    CAS  PubMed  Google Scholar 

  13. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23:56–62

    Article  CAS  Google Scholar 

  14. Hamilton M. Diagnosis and rating of anxiety. Br J Psychiatry Special Pub 1969; 3:76–79

    Google Scholar 

  15. Popescu A, Kao A. Neuropsychiatric systemic lupus erythematosus. Curr Neuropharmacol 2011; 9:449

    Article  CAS  Google Scholar 

  16. Jönsen A, Bengtsson A, Nived O, Ryberg B, Sturfelt G. Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality. Rheumatology 2002; 41:1308–1312

    Article  Google Scholar 

  17. Shehata G, Abdel-Kareem M, Yassin A, El Adl A. Sub-clinical cerebro-vascular cognitive function and mood changes in patients with systemic lupus erythematosus. Open Access Rheumatol 2010; 2:17–25

    Article  Google Scholar 

  18. Nery F, Borba E, Viana V, Hatch J, Soares J, Bonfá E, et al. Prevalence of depressive and anxiety disorders in systemic lupus erythematosus and their association with anti-ribosomal P antibodies. Prog Neuropsychopharmacology Biol Psychiatry 2008; 32:695–700

    Article  CAS  Google Scholar 

  19. Unterman A, Nolte J, Boaz M, Abady M, Shoenfeld Y, Zandman-Goddard G. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum 2011; 41:1–11

    Article  Google Scholar 

  20. Ainiala H, Dastidar P, Loukkola J, Lehtimäki T, Korpela M, Peltola J, et al. Cerebral MRI abnormalities and their association with neuro-psychiatric manifestations in SLE: a population-based study. Scand J Rheumatol 2005; 34:376–382

    Article  CAS  Google Scholar 

  21. Kheirandish M, Faezi ST, Paragomi P, Akhlaghi M, Gharibdoost F, Shahali A, et al. Prevalence and severity of depression and anxiety in patients with systemic lupus erythematosus: an epidemiologic study in Iranian patients. Mod Rheumatol 2014; 25:405–409

    Article  Google Scholar 

  22. Cavaco S, Martins da Silva A, Santos E, Coutinho E, Marinho A, Moreira I, et al. Are cognitive and olfactory dysfunctions in neuropsychiatric lupus erythematosus dependent on anxiety or depression? J Rheumatol 2012; 39:770–776

    Article  Google Scholar 

  23. Arinuma Y, Kikuchi H, Wada T, Nagai T, Tanaka S, Oba H, Hirohata S. Brain MRI in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Lupus Sci Med 2014; 1: e000050. doi: 10.1136/lupus-2014-000050s

    Article  Google Scholar 

  24. Jennings J, Sundgren P, Attwood J, McCune J, Maly P. Value of MRI of the brain in patients with systemic lupus erythematosus and neurologic disturbance. Neuroradiology 2004; 46:15–21

    Article  CAS  Google Scholar 

  25. Toubi E, Khamashta M, Panarra A, Hughes G. Association of antiphospholipid antibodies with central nervous system disease in systemic lupus erythematosus. Am J Med 1995; 99:397–401

    Article  CAS  Google Scholar 

  26. Shehata G, Elserogy Y, Ahmad H, Abdel-KareemM, Al-kabeer A, Rayan M, et al. Multimodal neurophysiological and psychometric evaluation among patients with systemic lupus erythematosus. Int J Gen Med 2011; 4:325

    Article  Google Scholar 

  27. Syuto T, Shimizu A, Takeuchi Y, Tanaka S, Hasegawa M, Nagai Y, et al. Association of antiphosphatidylserine/prothrombin antibodies with neuropsychiatric systemic lupus erythematosus. Clin Rheumatol 2009; 28:841–845

    Article  Google Scholar 

  28. Karassa F, loannidis J, Boki K. Risk factors for central nervous system involvement in systemic lupus erythematosus. J Rheumatol 2000; 93: 169–174

    CAS  Google Scholar 

  29. Sanna G, Bertolaccini M, Cuadrado M. Neuro-psychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol 2003; 30:985–992

    PubMed  Google Scholar 

  30. Nery F, Borba E, Hatch J, Soares J, Bonfá E, Neto F. Major depressive disorder and disease activity in systemic lupus erythematosus. Compr Psychiatry 2007; 48:14–19

    Article  Google Scholar 

  31. Toledano P, Sarbu N, Espinosa G, Bargalló N, Cervera R. Neuropsychiatric systemic lupus erythematosus: magnetic resonance imaging findings and correlation with clinical and immunological features. Autoimmunity Rev 2013; 12:1166–1170

    Article  Google Scholar 

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Authors and Affiliations

  1. Internal Medicine Department, Rheumatology Division, Ain Shams University, Egypt

    Caroline S. Morad (MD), Howaida E. Mansour & Shaimaa G. Arafa

  2. Rheumatology and Rehabilitation Department, Ain Shams University, Egypt

    Soha E. Ibrahim

  3. Radiodiagnosis Department, Ain Shams University, Egypt

    Khaled A. Ahmad

Authors
  1. Caroline S. Morad
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  2. Howaida E. Mansour
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  3. Soha E. Ibrahim
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  4. Khaled A. Ahmad
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  5. Shaimaa G. Arafa
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Corresponding author

Correspondence to Caroline S. Morad.

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Morad, C.S., Mansour, H.E., Ibrahim, S.E. et al. Subclinical neuropsychiatric dysfunctions in female patients with systemic lupus erythematosus. Egypt Rheumatol Rehabil 45, 49–56 (2018). https://doi.org/10.4103/err.err_46_17

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  • DOI: https://doi.org/10.4103/err.err_46_17

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