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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2018

Open Access 01-12-2018 | Research article

Altered white matter microstructure in lupus patients: a diffusion tensor imaging study

Authors: Jessika Nystedt, Markus Nilsson, Andreas Jönsen, Petra Nilsson, Anders Bengtsson, Åsa Lilja, Jimmy Lätt, Peter Mannfolk, Pia C Sundgren

Published in: Arthritis Research & Therapy | Issue 1/2018

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Abstract

Background

The purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms.

Methods

Structural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range 18.2–52.2 years) and 21 healthy controls (mean age 36.7 years, range 23.3–51.2 years) in conjunction with clinical examination, laboratory tests, cognitive evaluation, and self-assessment questionnaires. The patients were subgrouped according to the American College of Rheumatology Neuropsychiatric Systemic Lupus Erythematosus case definitions into non-neuropsychiatric SLE (nonNPSLE) and neuropsychiatric SLE (NPSLE).

Results

Comparisons between the SLE group and healthy controls showed that the mean fractional anisotropy (FA) was significantly reduced in the right rostral cingulum (p = 0.038), the mid-sagittal corpus callosum (CC) (p = 0.050), and the forceps minor of the CC (p = 0.015). The mean diffusivity (MD) was significantly increased in the left hippocampal cingulum (p = 0.017). No significant differences in MD or FA values were identified between NPSLE and nonNPSLE patients. Disease duration among all SLE patients correlated significantly with reduced FA in the CC (p < 0.05). No correlations were found between DTI parameters and white matter hyperintensities, SLE Disease Activity Index-2000, Systemic Lupus International Collaborating Clinical/ACR Organ Damage Index, or Montgomery Asberg Depression Rate Score Self-report.

Conclusions

We found alterations of white matter microstructure in SLE patients that were related to disease duration and fatigue. Our results indicate that cerebral involvement in SLE is not isolated to the NPSLE subgroup.
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Literature
1.
2.
3.
Bertsias GK, Boumpas DT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol. 2010;6:358–67.
4.
Hanly JG, Urowitz MB, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, Isenberg D, Alarcon GS, Clarke A, Bernatsky S, Merrill JT, Petri M, Dooley MA, Gladman D, Fortin PR, Steinsson K, Bruce I, Manzi S, Khamashta M, Zoma A, Aranow C, Ginzler E, Van Vollenhoven R, Font J, Sturfelt G, Nived O, Ramsey-Goldman R, Kalunian K, Douglas J, Thompson K, Farewell V, Systemic Lupus International Collaborating Clinics. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum. 2007;56(1):265–73.CrossRefPubMed
5.
Hanly JG, Urowitz MB, Su L, Bae SC, Gordon C, Wallace DJ, Clarke A, Bernatsky S, Isenberg D, Rahman A, Alarcón GS, Gladman DD, Fortin PR, Sanchez-Guerrero J, Romero-Diaz J, Merrill JT, Ginzler E, Bruce IN, Steinsson K, Khamashta M, Petri M, Manzi S, Dooley MA, Ramsey-Goldman R, Van Vollenhoven R, Nived O, Sturfelt G, Aranow C, Kalunian K, Ramos-Casals M, Zoma A, Douglas J, Thompson K, Farewell V. Prospective analysis of neuropsychiatric events in an international disease inception cohort of SLE patients. Ann Rheum Dis. 2010;69(3):529–35.CrossRefPubMed
6.
Jonsen A, Bengtsson AA, Nived O, Ryberg B, Sturfelt G. Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality. Rheumatology (Oxford). 2002;41(11):1308–12.CrossRef
7.
Zirkzee EJM, Huizinga TWJ, Bollen ELEM, Buchem MA, Middelkoop HAM, Wee NJA. Mortality in neurops ychiatric systemic lupus erythematosus (NPSLE). Lupus. 2014;23(1):31–8.
8.
Ainiala H, Loukkola J, Peltola J, Korpela M, Hietaharju A. The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology. 2001;57(3):496–500.
9.
Fisk JD, Eastwood B, Sherwood G, Hanly JG. Patterns of cognitive impairment in patients with systemic lupus erythematosus. Br J Rheumatol. 1993;32:458–62.
10.
Hanly JG, Fisk JD, Sherwood G, Eastwood B. Clinical course of cognitive dysfunction in systemic lupus erythematosus. J Rheumatol. 1994;21:1825–31.
11.
Ho RC, Thiaghu C, Ong H, Lu Y, Ho CS, Tam WW, Zhang MW. A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus. Autoimmun Rev. 2016;15(2):124–38.CrossRefPubMed
12.
Kivity S, Katzav A, Arango MT, Landau-Rabi M, Zafrir Y, Agmon-Levin N. 16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus. BMC Med. 2013;11:90. https://​doi.​org/​10.​1186/​1741-7015-11-90.
13.
Gulati G, Jones JT, Lee G, Altaye M, Beebe DW, Meyers-Eaton J, Wiley K, Brunner HI, DiFrancesco MW. Blood brain barrier permeability is altered in patients with systemic lupus erythematosus: a novel imaging approach. Arthritis Care Res (Hoboken). 2017;69(2):299–305.26.
14.
Conti F, Alessandri C, Perricone C, Scrivo R, Rezai S, Ceccarelli F, Spinelli FR, Ortona E, Marianetti M, Mina C, Valesini G. Neurocognitive dysfunction in systemic lupus erythematosus: association with antiphospholipid antibodies, disease activity and chronic damage. PLoS One. 2012;7(3):e33824.CrossRefPubMedPubMedCentral
15.
16.
Hanly JG. Attribution in the assessment of nervous system disease in SLE. Rheumatology (Oxford). 2015;54(5):755–6.CrossRef
17.
Jennings JE, Sundgren PC, Attwood J, McCune J, Maly P. Value of MRI of the brain in patients with systemic lupus erythematosus and neurologic disturbance. Neuroradiology. 2004;46(1):15–21.CrossRefPubMed
18.
Sarbu N, Alobeidi F, Toledano P, Espinosa G, Giles I, Rahman A, Yousry T, Capurro S, Jäger R, Cervera R, Bargalló N. 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.CrossRefPubMed
19.
Ainiala H, Dastidar P, Loukkola J, Lehtimaki T, Korpela M, Peltola J, Hietaharju A. Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population-based study. Scand J Rheumatol. 2005;34(5):376–82.CrossRefPubMed
20.
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. Autoimmun Rev. 2013;12(12):1166–70.CrossRefPubMed
21.
Beaulieu C. The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed. 2002;15(7–8):435–55.CrossRefPubMed
22.
Sjolund J, Szczepankiewicz F, Nilsson M, Topgaard D, Westin CF, Knutsson H. Constrained optimization of gradient waveforms for generalized diffusion encoding. J Magn Reson. 2015;261:157–68.CrossRefPubMedPubMedCentral
23.
Douaud G, Jbabdi S, Behrens TE, Menke RA, Gass A, Monsch AU, Rao A, Whitcher B, Kindlmann G, Matthews PM, Smith S. DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease. Neuroimage. 2011;55(3):880–90.CrossRefPubMed
24.
Bressler SL, Menon V. Large-scale brain networks in cognition: emerging methods and principles. Trends Cogn Sci. 2010;14(6):277–90.CrossRefPubMed
25.
Metzler-Baddeley C, Jones DK, Steventon J, Westacott L, Aggleton JP, O'Sullivan MJ. Cingulum microstructure predicts cognitive control in older age and mild cognitive impairment. J Neurosci. 2012;32(49):17612–9.CrossRefPubMed
26.
Shapira-Lichter I, Weinstein M, Lustgarten N, Ash E, Litinsky I, Aloush V, Anouk M, Caspi D, Hendler T, Paran D. Impaired diffusion tensor imaging findings in the corpus callosum and cingulum may underlie impaired learning and memory abilities in systemic lupus erythematosus. Lupus. 2016;25(11):1200–8.
27.
Thiebaut de Schotten M, Ffytche DH, Bizzi A, Dell'Acqua F, Allin M, Walshe M, Murray R, Williams SC, Murphy DG, Catani M. Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography. Neuroimage. 2011;54(1):49–59.CrossRefPubMed
28.
Catani M, Thiebaut de Schotten M. A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex. 2008;44(8):1105–32.CrossRefPubMed
29.
Emmer BJ, Veer IM, Steup-Beekman GM, Huizinga TW, van der Grond J, van Buchem MA. Tract-based spatial statistics on diffusion tensor imaging in systemic lupus erythematosus reveals localized involvement of white matter tracts. Arthritis Rheum. 2010;62(12):3716–21.CrossRefPubMed
30.
Potapov AA, Goryainov SA, Zhukov VY, Pitskhelauri DI, Kobyakov GL, Pronin IN, Zakharova NE, Tanoyan AA, Ogurtsova AA, Buklina SB, Melikyan ZA. The long-associative pathway of the white matter: modern view from the perspective of neuroscience. Zh Vopr Neirokhir Im N N Burdenko. 2014;78(5):66–77. discussion 77.PubMed
31.
Schmidt-Wilcke T, Cagnoli P, Wang P, Schultz T, Lotz A, McCune WJ, Sundgren PC. Diminished white matter integrity in patients with systemic lupus erythematosus. Neuroimage Clin. 2014;5:291–7.CrossRefPubMedPubMedCentral
32.
Shastri R, Shah G, Wang P, Cagnoli P, Schmidt-Wilcke T, McCune J, Harris R, Sundgren P. MR diffusion tractography to identify and characterize microstructural white matter tract changes in systemic lupus erythematosus patients. Acad Radiol. 2016;23(11):1431–40.CrossRefPubMed
33.
34.
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992;35(6):630–40.CrossRefPubMed
35.
Fantino B, Moore N. The self-reported Montgomery-Asberg Depression Rating Scale is a useful evaluative tool in Major Depressive Disorder. BMC Psychiatry. 2009;9:26.CrossRefPubMedPubMedCentral
36.
Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–9.CrossRefPubMed
37.
Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121–3.CrossRefPubMed
38.
Gualtieri CT, Johnson LG. Reliability and validity of a computerized neurocognitive test battery, CNS Vital Signs. Arch Clin Neuropsychol. 2006;21(7):623–43.CrossRefPubMed
39.
Gualtieri CT, Johnson LG. A computerized test battery sensitive to mild and severe brain injury. Medscape J Med. 2008;10(4):90.PubMedPubMedCentral
40.
Littleton AC, Register-Mihalik JK, Guskiewicz KM. Test-retest reliability of a computerized concussion test: CNS Vital Signs. Sports Health. 2015;7(5):443–7.CrossRefPubMedPubMedCentral
41.
Meskal I, Gehring K, van der Linden SD, Rutten GJ, Sitskoorn MM. Cognitive improvement in meningioma patients after surgery: clinical relevance of computerized testing. J Neurooncol. 2015;121(3):617–25.CrossRefPubMed
42.
Papathanasiou A, Messinis L, Georgiou VL, Papathanasopoulos P. Cognitive impairment in relapsing remitting and secondary progressive multiple sclerosis patients: efficacy of a computerized cognitive screening battery. ISRN Neurol. 2014;2014:151379.CrossRefPubMedPubMedCentral
43.
Hanly JG, Omisade A, Su L, Farewell V, Fisk JD. Assessment of cognitive function in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis by computerized neuropsychological tests. Arthritis Rheum. 2010;62(5):1478–86.CrossRefPubMedPubMedCentral
44.
Kozora E, Erkan D, West SG, Filley CM, Zhang L, Ramon G, Duggan E, Lockshin MD. Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE). Lupus. 2013;22(1):73–80.CrossRefPubMed
45.
Klein S, Staring M, Murphy K, Viergever MA, Pluim JP. elastix: a toolbox for intensity-based medical image registration. IEEE Trans Med Imaging. 2010;29(1):196–205.CrossRefPubMed
46.
Nilsson M, Szczepankiewicz F, van Westen D, Hansson O. Extrapolation-based references improve motion and eddy-current correction of high B-value DWI data: application in Parkinson's disease dementia. PLoS One. 2015;10(11):e0141825.CrossRefPubMedPubMedCentral
47.
Tournier JD, Calamante F, Gadian DG, Connelly A. Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution. Neuroimage. 2004;23(3):1176–85.CrossRefPubMed
48.
Andersson JLR, Jenkinson M, Smith S (2010) Non-linear registration, aka spatial normalisation. FMRIB technical report TR07JA2.
49.
Mackay M, Bussa MP, Aranow C, Ulug AM, Volpe BT, Huerta PT, Argyelan M, Mandel A, Hirsch J, Diamond B, Eidelberg D. 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.
50.
Hughes M, Sundgren PC, Fan X, Foerster B, Nan B, Welsh RC, Williamson JA, Attwood J, Maly PV, Chenevert TL, McCune W, Gebarski S. 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(2):213–22.CrossRefPubMed
51.
Filley CM, Kozora E, Brown MS, Miller DE, West SG, Arciniegas DB, Grimm A, Zhang L. White matter microstructure and cognition in non-neuropsychiatric systemic lupus erythematosus. Cogn Behav Neurol. 2009;22(1):38–44.CrossRefPubMed
52.
Sarbu N, Toledano P, Calvo A, Roura E, Sarbu MI, Espinosa G, Llado X, Cervera R, Bargallo N. Advanced MRI techniques: biomarkers in neuropsychiatric lupus. Lupus. 2017;26(5):510–6.CrossRefPubMed
53.
Kozora E, Arciniegas DB, Filley CM, West SG, Brown M, Miller D, Grimm A, Devore MD, Wingrove C, Zhang L. Cognitive and neurologic status in patients with systemic lupus erythematosus without major neuropsychiatric syndromes. Arthritis Care Res. 2008;59(11):1639–46.CrossRef
54.
Kozora E, Filley CM. Cognitive dysfunction and white matter abnormalities in systemic lupus erythematosus. J Int Neuropsychol Soc. 2011;17(3):385–92.CrossRefPubMed
55.
Kozora E, Hanly JG, Lapteva L, Filley CM. Cognitive dysfunction in systemic lupus erythematosus: past, present, and future. Arthritis Rheum. 2008;58(11):3286–98.CrossRefPubMed
56.
Benedict RHB, Shucard JL, Zivadinov R, Shucard DW. Neuropsychological impairment in systemic lupus erythematosus: a comparison with multiple sclerosis. Neuropsychol Rev. 2008;18(2):149–66.CrossRefPubMedPubMedCentral
Metadata
Title
Altered white matter microstructure in lupus patients: a diffusion tensor imaging study
Authors
Jessika Nystedt
Markus Nilsson
Andreas Jönsen
Petra Nilsson
Anders Bengtsson
Åsa Lilja
Jimmy Lätt
Peter Mannfolk
Pia C Sundgren
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2018
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-018-1516-0

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