title: Diminished white matter integrity in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25-70% of patients. Using diffusion tensor imaging (DTI) various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate, if regional changes in white matter integrity can also be detected in SLE patients without neuropsychiatric symptoms (non-NPSLE patients).
  
  
  METHODS
  Applying DTI and tract based spatial statistics (TBSS) we investigated 19 NPSLE patients, 19 non-NPSLE and 18 healthy controls. Groups were matched for age and sex. Image pre-processing was performed using FSL, following the TBSS pipeline (eddy current correction, estimation of fractional anisotropy (FA), normalization, skeletonization of the group mean FA image). A general linear model with threshold-free cluster enhancement was used to assess significant differences between the three groups.
  
  
  RESULTS
  Statistical analyses revealed several regions of decreased prefrontal white matter integrity (decreased FA) in both groups of SLE patients. The changes found in the non-NPSLE patients (as compared to healthy controls) overlapped with those in the NPSLE patients, but were not as pronounced.
  
  
  CONCLUSIONS
  Our data suggest that changes in regional white matter integrity, in terms of a decrease in FA, are present not only in NPSLE patients, but also in non-NPSLE patients, though to a lesser degree. We also demonstrate that the way statistical maps are corrected for multiple comparisons has a profound influence on whether alterations in white matter integrity in non-NPSLE patients are deemed significant.
authors.affiliation: Department of Neurology, Berufsgenossenschaftliche Universitätsklinik, Ruhr Universität Bochum, Bochum, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmidt-Wilcke
authors.affiliation: Department of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cagnoli
authors.affiliation: Department of Diagnostic Radiology, University of Michigan Hospital, Ann Arbor, USA.
authors.forename: Page
authors.initials: P
authors.lastname: Wang
authors.affiliation: Max Planck Institute for Intelligent Systems, Tübingen, Germany ; Department of Computer Science, University of Bonn, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schultz
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Ruhr Universität Bochum, Bochum, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Lotz
authors.affiliation: Department of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Mccune
authors.affiliation: Department of Diagnostic Radiology, University of Michigan Hospital, Ann Arbor, USA ; Department of Radiology, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Pia C
authors.initials: PC
authors.lastname: Sundgren
mesh_terms: D000328:Adult; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008180:Lupus Erythematosus, Systemic / Q000473:pathology*; D020945:Lupus Vasculitis, Central Nervous System / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: ACR, American College of Rheumatology; CNS, central nervous system; DTI, diffusion tensor imaging; Diffusion tensor imaging; FA, fractional anisotropy; MRI, magnetic resonance imaging; SD, standard deviation; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; SLICC, systemic lupus erythematosus International Collaborating Clinics; SVM, support vector machine; Systemic lupus erythematosus; TBSS, tract based spatial statistics; TFCE, threshold free cluster enhancement; VBM, voxel based morphometry; White matter; dMRI, diffusion MRI