European Radiology

, Volume 26, Issue 4, pp 959–968 | Cite as

Diffusion tensor imaging in patients with obstetric antiphospholipid syndrome without neuropsychiatric symptoms

  • Fabricio R. Pereira
  • Francesco Macri
  • Marcel P. Jackowski
  • William J. Kostis
  • Jean-Christophe Gris
  • Jean-Paul Beregi
  • Choukri MekkaouiEmail author
Magnetic Resonance



To evaluate white matter (WM) integrity in neurologically asymptomatic antiphospholipid syndrome (APS) using diffusion tensor imaging (DTI) in women with no thrombotic history but with pregnancy loss.


Imaging was performed with a 3 T scanner using structural MRI (T1-weighted, fluid attenuation inversion recovery [FLAIR]) and DTI sequences in 66 women with APS and a control group of 17 women. Women with APS were further categorized as positive for lupus anticoagulant (LA) and/or aβ2GPI-G antibodies (LA/aβ2GPI-G-positive, N = 29) or negative (LA/aβ2GPI-G-negative, N = 37) for both. Tract-based spatial statistics of standard DTI-based indices were compared among groups.


Women with APS had significantly lower fractional anisotropy (p < 0.05) associated with higher mean diffusivity and radial diffusivity compared to the control group. There was a stronger association of abnormal DTI features among women positive for LA and/or aβ2GPI-IgG antibodies than those who were negative.


DTI appears sensitive to subtle WM changes in women with APS with no thrombotic history but with pregnancy loss, compatible with alterations in axonal structure and in the myelin sheath. The preferential association of abnormal DTI features with the two most pathogenic aPLAbs reinforces the pathophysiological relevance of our findings.

Key Points

• APS women exhibited lower FA and higher MD and RD than controls.

• WM impairments are more severe in patients with positive LA or aβ2GPI-IgG.

• An association exists between abnormal DTI features and LA or aβ2GPI-IgG positivity.

• Diffusion tensor imaging detects microstructural white matter abnormalities in APS women.


Diffusion tensor imaging Magnetic resonance imaging White matter Antiphospholipid syndrome Pregnancy 



Antiphospholipid syndrome


Antiphospholipid antibodies


Lupus anticoagulant


Anticardiolipin antibodies


Anti-β2-glycoprotein I antibodies


Central nervous system


White matter


Fractional anisotropy


Mean diffusivity


Radial diffusivity


Nîmes Obstetricians and Hematologists Antiphospholipid Syndrome


Analysis of Functional NeuroImages


Tract-based spatial statistics


Threshold-free cluster enhancement



The authors thank all the study participants who agreed to join us in this long-term NOHA (Nîmes Obstetricians and Haematologists Antiphospholipid) administrative region-hospital medical network) adventure. We are also grateful to the NOHA network of gynaecologists, obstetricians and general practitioners who actively contributed to the study. We also thank the research staff of the Delegation for Clinical Research and Innovation of the University Hospital of Nîmes for their active help and support (N. Best, S. Granier, B. Lafont, C. Masseguin, H. Obert, H. Léal, O. Albert).

The scientific guarantor of this publication is Dr. Fabricio R. Pereira. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. One of the authors (Fabricio R. Pereira) has significant statistical expertise. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective, case–control study, performed at one institution.


  1. 1.
    Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306CrossRefPubMedGoogle Scholar
  2. 2.
    Gris JC, Brenner B (2013) Antiphospholipid antibodies: neuropsychiatric presentations. Semin Thromb Hemost 39:935–942CrossRefPubMedGoogle Scholar
  3. 3.
    Mayer M, Cerovec M, Rados M, Cikes N (2010) Antiphospholipid syndrome and central nervous system. Clin Neurol Neurosurg 112:602–608CrossRefPubMedGoogle Scholar
  4. 4.
    Gris JC, Bouvier S, Molinari N et al (2012) Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood 119:2624–2632CrossRefPubMedGoogle Scholar
  5. 5.
    Provenzale JM, Barboriak DP, Allen NB, Ortel TL (1996) Patients with antiphospholipid antibodies: CT and MR findings of the brain. AJR Am J Roentgenol 167:1573–1578CrossRefPubMedGoogle Scholar
  6. 6.
    Provenzale JM, Ortel TL, Allen NB (1998) Systemic thrombosis in patients with antiphospholipid antibodies: lesion distribution and imaging findings. AJR Am J Roentgenol 170:285–290CrossRefPubMedGoogle Scholar
  7. 7.
    Le Bihan D, Mangin JF, Poupon C et al (2001) Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging 13:534–546CrossRefPubMedGoogle Scholar
  8. 8.
    Mori S, Zhang J (2006) Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron 51:527–539CrossRefPubMedGoogle Scholar
  9. 9.
    Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8:333–344CrossRefPubMedGoogle Scholar
  10. 10.
    Stosic M, Ambrus J, Garg N et al (2010) MRI characteristics of patients with antiphospholipid syndrome and multiple sclerosis. J Neurol 257:63–71CrossRefPubMedGoogle Scholar
  11. 11.
    Wheeler-Kingshott CA, Cercignani M (2009) About "axial" and "radial" diffusivities. Magn Reson Med 61:1255–1260CrossRefPubMedGoogle Scholar
  12. 12.
    Sheehan DV, Lecrubier Y, Sheehan KH et al (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33, quiz 34–57 PubMedGoogle Scholar
  13. 13.
    Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29:162–173CrossRefPubMedGoogle Scholar
  14. 14.
    Haselgrove JC, Moore JR (1996) Correction for distortion of echo-planar images used to calculate the apparent diffusion coefficient. Magn Reson Med 36:960–964CrossRefPubMedGoogle Scholar
  15. 15.
    Jenkinson M, Bannister P, Brady M, Smith S (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17:825–841CrossRefPubMedGoogle Scholar
  16. 16.
    Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17:143–155CrossRefPubMedGoogle Scholar
  17. 17.
    Smith SM, Jenkinson M, Johansen-Berg H et al (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:1487–1505CrossRefPubMedGoogle Scholar
  18. 18.
    Carmack PS, Spence J, Gunst RF, Schucany WR, Woodward WA, Haley RW (2004) Improved agreement between Talairach and MNI coordinate spaces in deep brain regions. Neuroimage 22:367–371CrossRefPubMedGoogle Scholar
  19. 19.
    Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: A primer with examples. Hum Brain Mapp 15:1–25CrossRefPubMedGoogle Scholar
  20. 20.
    Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44:83–98CrossRefPubMedGoogle Scholar
  21. 21.
    Schultz T, Kindlmann GL (2010) Superquadric glyphs for symmetric second-order tensors. IEEE Trans Vis Comput Graph 16:1595–1604CrossRefPubMedGoogle Scholar
  22. 22.
    Asherson RA, Derksen RH, Harris EN et al (1987) Chorea in systemic lupus erythematosus and "lupus-like" disease: association with antiphospholipid antibodies. Semin Arthritis Rheum 16:253–259CrossRefPubMedGoogle Scholar
  23. 23.
    Brey RL, Escalante A (1998) Neurological manifestations of antiphospholipid antibody syndrome. Lupus 7:S67–74CrossRefPubMedGoogle Scholar
  24. 24.
    Chapman J, Rand JH, Brey RL et al (2003) Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies. Lupus 12:514–517CrossRefPubMedGoogle Scholar
  25. 25.
    Khamashta MA, Gil A, Anciones B et al (1988) Chorea in systemic lupus erythematosus: association with antiphospholipid antibodies. Ann Rheum Dis 47:681–683CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sanna G, Bertolaccini ML, Cuadrado MJ et al (2003) Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol 30:985–992PubMedGoogle Scholar
  27. 27.
    Khalili A, Cooper RC (1991) A study of immune responses to myelin and cardiolipin in patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 85:365–372CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Rodrigues CE, Carvalho JF, Shoenfeld Y (2010) Neurological manifestations of antiphospholipid syndrome. Eur J Clin Invest 40:350–359CrossRefPubMedGoogle Scholar
  29. 29.
    Sun KH, Liu WT, Tsai CY, Liao TS, Lin WM, Yu CL (1992) Inhibition of astrocyte proliferation and binding to brain tissue of anticardiolipin antibodies purified from lupus serum. Ann Rheum Dis 51:707–712CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Katzav A, Pick CG, Korczyn AD et al (2001) Hyperactivity in a mouse model of the antiphospholipid syndrome. Lupus 10:496–499CrossRefPubMedGoogle Scholar
  31. 31.
    Ziporen L, Shoenfeld Y, Levy Y, Korczyn AD (1997) Neurological dysfunction and hyperactive behavior associated with antiphospholipid antibodies. A mouse model. J Clin Invest 100:613–619CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Frauenknecht K, Katzav A, Grimm C, Chapman J, Sommer CJ (2013) Neurological impairment in experimental antiphospholipid syndrome is associated with increased ligand binding to hippocampal and cortical serotonergic 5-HT1A receptors. Immunobiology 218:517–526CrossRefPubMedGoogle Scholar
  33. 33.
    Shrot S, Katzav A, Korczyn AD et al (2002) Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies. Lupus 11:736–743CrossRefPubMedGoogle Scholar
  34. 34.
    Liu Y, Spulber G, Lehtimaki KK et al (2011) Diffusion tensor imaging and tract-based spatial statistics in Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 32:1558–1571CrossRefPubMedGoogle Scholar
  35. 35.
    Saini J, Bagepally BS, Bhatt MD et al (2012) Diffusion tensor imaging: tract based spatial statistics study in essential tremor. Parkinsonism Relat Disord 18:477–482CrossRefPubMedGoogle Scholar
  36. 36.
    Fernandez-Fernandez FJ, Rivera-Gallego A, de la Fuente-Aguado J, Perez-Fernandez S, Munoz-Fernandez D (2006) Antiphospholipid syndrome mimicking multiple sclerosis in two patients. Eur J Intern Med 17:500–502CrossRefPubMedGoogle Scholar
  37. 37.
    Ioannidis P, Maiovis P, Balamoutsos G, Karacostas D (2014) Primary antiphospholipid syndrome mimicking demyelinating disorders. J Neuropsychiatry Clin Neurosci 26:E54–55CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2015

Authors and Affiliations

  • Fabricio R. Pereira
    • 1
  • Francesco Macri
    • 1
    • 2
  • Marcel P. Jackowski
    • 3
  • William J. Kostis
    • 4
    • 5
  • Jean-Christophe Gris
    • 2
    • 6
  • Jean-Paul Beregi
    • 1
    • 2
  • Choukri Mekkaoui
    • 1
    • 2
    • 4
    • 5
    Email author
  1. 1.Department of RadiologyUniversity Hospital Center of Nîmes and Research Team EA 2415NîmesFrance
  2. 2.Faculty of MedicineMontpellier UniversityMontpellierFrance
  3. 3.Department of Computer Science, Institute of Mathematics and StatisticsUniversity of São PauloSão PauloBrazil
  4. 4.Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  5. 5.Athinoula A. Martinos Center for Biomedical ImagingCharlestownUSA
  6. 6.Department and Laboratory of HematologyUniversity Hospital Center of NîmesNîmesFrance

Personalised recommendations