Brain Single Photon Emission Computed Tomography Scan (SPECT) and Functional MRI in Systemic Lupus Erythematosus Patients with Cognitive Dysfunction: A Systematic Review

Document Type : Review article


1 Rheumatic Diseases Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Radiology, School of Medicine, Mashhad University of Medical Sciences; Mashhad, Iran


Objective(s): Systemic lupus erythematosus (SLE) is an autoimmune disease with a wide range of clinical manifestations. Cognitive dysfunction is one of the manifestations that could present prior to the emergence of any other neuropsychiatric involvements in SLE. Cognitive dysfunction is a subtle condition occurring with a
high frequency. However, there is no data on the correlation of cognitive dysfunction with central nervous system (CNS) imaging findings, in particular single-photon emission computed tomography scan (SPECT) and functional MRI. We decided to perform a systematic review of brain SPECT and fMRI in SLE patients with cognitive dysfunction.
Methods: PubMed, Scopus, and Google Scholar databases were searched until April 2017 with the following keywords: “SLE OR systemic lupus erythematous OR lupus” AND “functional MRI OR functional magnetic resonance imaging OR fMRI OR SPECT or SCAN”. A total of 1,767articles were found. Two rheumatologists
reviewed the articles and finally 14 articles were selected for the final systematic review.
Results: The fMRI and SPECT imaging techniques could provide valuable information regarding the SLE patients with cognitive dysfunction at the early stages of the disease.
Conclusion: Brain SPECT scan and fMRI are used as functional imaging tools in SLE. Both of these diagnostic modalities are sensitive in reflecting the subtle brain damages in SLE patients with cognitive dysfunction. Brain fMRI and SPECT scan could be significantly beneficial in the diagnosis and initial management of cognitive dysfunction in SLE. Nevertheless, prospective studies could be useful in confirming the application of these diagnostic modalities in the clinical setting.


Main Subjects

  1. Meszaros ZS, Perl A, Faraone SV. Psychiatric symptoms in systemic lupus erythematosus: a systematic review. J Clin Psychiatry. 2012;73(7):993-1001.
  2. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42(4):599-608.
  3. Peretti CS, Peretti CR, Kozora E, Papathanassiou D, Chouinard VA, Chouinard G. Cognitive impairment in systemic lupus erythematosus women with elevated autoantibodies and normal single photon emission computerized tomography. Psychother Psychosom. 2012;81(5):276-85.
  4. Kozora E, Laudenslager M, Lemieux A, West SG. Inflammatory and hormonal measures predict neuropsychological functioning in systemic lupus erythematosus and rheumatoid arthritis patients. J Int Neuropsychol Soc. 2001;7(6):745-54.
  5. Sankowski R, Mader S, Valdes-Ferrer SI. Systemic inflammation and the brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration. Front Cell Neurosci. 2015;9:28.
  6. Petri M, Naqibuddin M, Carson KA, Sampedro M, Wallace DJ, Weisman MH, et al. Cognitive function in a systemic lupus erythematosus inception cohort. J Rheumatol. 2008;35(9):1776-81.
  7. Lopez-Longo FJ, Carol N, Almoguera MI, Olazaran J, Alonso-Farto JC, Ortega A, et al. Cerebral hypoperfusion detected by SPECT in patients with systemic lupus erythematosus is related to clinical activity and cumulative tissue damage. Lupus. 2003;12(11):813-9.
  8. Sanna G, Piga M, Terryberry JW, Peltz MT, Giagheddu S, Satta L, et al. Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations. Lupus. 2000;9(8):573-83.
  9. Phillips B, Ball C, Badenoch D, Straus S, Haynes B, Dawes M. Oxford centre for evidence-based medicine levels of evidence (May 2001). BJU Int. 2011;107(5):870.

10. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.

11. Brey R, Holliday S, Saklad A, Navarrete M, Hermosillo-Romo D, Stallworth C, et al. Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology. 2002;58(8):1214-20.

12. DiFrancesco MW, Holland SK, Ris MD, Adler CM, Nelson S, DelBello MP, et al. Functional magnetic resonance imaging assessment of cognitive function in childhood-onset systemic lupus erythematosus: a pilot study. Arthritis Rheum. 2007;56(12):4151-63.

13. Fitzgibbon B, Fairhall S, Kirk I, Kalev-Zylinska M, Pui K, Dalbeth N, et al. Functional MRI in NPSLE patients reveals increased parietal and frontal brain activation during a working memory task compared with controls. Rheumatology. 2007;47(1):50-3.

14. Shapira-Lichter I, Vakil E, Litinsky I, Oren N, Glikmann-Johnston Y, Caspi D, et al. Learning and memory-related brain activity dynamics are altered in systemic lupus erythematosus: a functional magnetic resonance imaging study. Lupus. 2013;22(6):562-73.

15. Al-Obaidi M, Saunders D, Brown S, Ramsden L, Martin N, Moraitis E, et al. Evaluation of magnetic resonance imaging abnormalities in juvenile onset neuropsychiatric systemic lupus erythematosus. Clin Rheumatol. 2016;35(10):2449-56.

16. Piga M, Peltz MT, Montaldo C, Perra D, Sanna G, Cauli A, et al. Twenty-year brain magnetic resonance imaging follow-up study in systemic lupus erythematosus: factors associated with accrual of damage and central nervous system involvement. Autoimmun Rev. 2015;14(6):510-6.

17. Cesar B, Dwyer MG, Shucard JL, Polak P, Bergsland N, Benedict RH, et al. Cognitive and white matter tract differences in MS and diffuse neuropsychiatric systemic lupus erythematosus. AJNR Am J Neuroradiol. 2015;36(10):1874-83.

18. Zimmermann N, Corrêa DG, Kubo TA, Netto TM, Pereira DB, Fonseca RP, et al. Global cognitive impairment in systemic lupus erythematosus patients: a structural MRI study. Clin Neuroradiol. 2017;27(1):23-9.

19. Sarbu N, Alobeidi F, Toledano P, Espinosa G, Giles I, Rahman A, et al. Brain abnormalities in newly diagnosed neuropsychiatric lupus: systematic MRI approach and correlation with clinical and laboratory data in a large multicenter cohort. Autoimmun Rev. 2015;14(2):153-9.

20. Ichinose K, Arima K, Ushigusa T, Nishino A, Nakashima Y, Suzuki T, et al. Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases. Clin Immunol. 2015;157(2):114-20.

21. Nishimura K, Omori M, Katsumata Y, Sato E, Gono T, Kawaguchi Y, et al. Neurocognitive impairment in corticosteroid-naive patients with active systemic lupus erythematosus: a prospective study. J Rheumatol. 2015;42(3):441-8.

22. Driver CB, Wallace DJ, Lee JC, Forbess CJ, Pourrabbani S, Minoshima S, et al. Clinical validation of the watershed sign as a marker for neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 2008;59(3):332-7.

23. Oh D, Kim S, Jung S, Sung Y, Bang S, Bae S, et al. Precuneus hypoperfusion plays an important role in memory impairment of patients with systemic lupus erythematosus. Lupus. 2011;20(8):855-60.

24. Zhang X, Zhu Z, Zhang F, Shu H, Li F, Dong Y. 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(6):845-9.

25. Waterloo K, Omdal R, Sjoholm H, Koldingsnes W, Jacobsen EA, Sundsfjord JA, et al. Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow. J Neurol. 2001;248(7):595-602.

26. Mackay M, Bussa MP, Aranow C, Uluğ AM, Volpe BT, Huerta PT, et al. Differences in regional brain activation patterns assessed by functional magnetic resonance imaging in patients with systemic lupus erythematosus stratified by disease duration. Mol Med. 2011;17(11-12): 1349-56.

27. Rocca MA, Agosta F, Mezzapesa DM, Ciboddo G, Falini A, Comi G, et al. An fMRI study of the motor system in patients with neuropsychiatric systemic lupus erythematosus. Neuroimage. 2006;30(2):478-84.

28. Maeshima E, Yamada Y, Yukawa S, Nomoto H. Higher cortical dysfunction, antiphospholipid antibodies and neuroradiological examinations in systemic lupus erythematosus. Intern Med. 1992;31(10):1169-74.

29. Kao CH, Ho YJ, Lan JL, Changlai SP, Liao KK, Chieng PU. 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(1):61-8.

30. Sun SS, Huang WS, Chen JJ, Chang CP, Kao CH, Wang JJ. Evaluation of the effects of methylprednisolone pulse therapy in patients with systemic lupus erythematosus with brain involvement by Tc-99m HMPAO brain SPECT. Eur Radiol. 2004;14(7): 1311-5.

31. Liu FY, Huang WS, Kao CH, Yen RF, Wang JJ, Ho ST. Usefulness of Tc-99m ECD brain SPECT to evaluate the effects of methylprednisolone pulse therapy in lupus erythematosus with brain involvement: a preliminary report. Rheumatol Int. 2003;23(4):182-5.

32. Castellino G, Padovan M, Bortoluzzi A, Borrelli M, Feggi L, Caniatti ML, et al. Single photon emission computed tomography and magnetic resonance imaging evaluation in SLE patients with and without neuropsychiatric involvement. Rheumatology. 2008;47(3):319-23.

33. Strakowski SM, Adler CM, Holland SK, Mills N, DelBello MP. A preliminary FMRI study of sustained attention in euthymic, unmedicated bipolar disorder. Neuropsychopharmacology. 2004;29(9):1734-40.

34. McKiernan KA, D’Angelo BR, Kaufman JN, Binder JR. Interrupting the “stream of consciousness”: an fMRI investigation. Neuroimage. 2006;29(4): 1185-91.

35. Weinberger DR, Mattay V, Callicott J, Kotrla K, Santha A, van Gelderen P, et al. fMRI applications in schizophrenia research. Neuroimage. 1996;4(3 Pt 3):S118-26.

36. Chen JJ, Yen RF, Kao A, Lin CC, Lee CC. Abnormal regional cerebral blood flow found by technetium-99m ethyl cysteinate dimer brain single photon emission computed tomography in systemic lupus erythematosus patients with normal brain MRI findings. Clin Rheumatol. 2002;21(6):516-9.

37. Lin WY, Wang SJ, Yen TC, Lan JL. Technetium-99m-HMPAO brain SPECT in systemic lupus erythematosus with CNS involvement. J Nucl Med. 1997;38(7):1112-5.